{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T22:00:03Z","timestamp":1792533603984,"version":"4.5.0"},"reference-count":228,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T00:00:00Z","timestamp":1610150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI18\/01519"],"award-info":[{"award-number":["PI18\/01519"]}]},{"name":"Spanish Ministry of Science, Innovation and Universities","award":["SAF2017-85146-R"],"award-info":[{"award-number":["SAF2017-85146-R"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Multiple myeloma (MM) is a hematologic cancer characterized by clonal proliferation of plasma cells in the bone marrow (BM). The progression, from the early stages of the disease as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to MM and occasionally extramedullary disease, is drastically affected by the tumor microenvironment (TME). Soluble factors and direct cell\u2013cell interactions regulate MM plasma cell trafficking and homing to the BM niche. Mesenchymal stromal cells, osteoclasts, osteoblasts, myeloid and lymphoid cells present in the BM create a unique milieu that favors MM plasma cell immune evasion and promotes disease progression. Moreover, TME is implicated in malignant cell protection against anti-tumor therapy. This review describes the main cellular and non-cellular components located in the BM, which condition the immunosuppressive environment and lead the MM establishment and progression.<\/jats:p>","DOI":"10.3390\/cancers13020217","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T19:55:56Z","timestamp":1610308556000},"page":"217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":234,"title":["The Role of Tumor Microenvironment in Multiple Myeloma Development and Progression"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5345-7990","authenticated-orcid":false,"given":"Almudena","family":"Garc\u00eda-Ortiz","sequence":"first","affiliation":[{"name":"Hematology Department, Hospital 12 de Octubre, i+12, CNIO, CIBERONC, ES 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaiza","family":"Rodr\u00edguez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedicine, Centro de Investigaciones Biol\u00f3gicas, CSIC, ES 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4479-9822","authenticated-orcid":false,"given":"Jessica","family":"Encinas","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital 12 de Octubre, i+12, CNIO, CIBERONC, ES 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Maroto-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital 12 de Octubre, i+12, CNIO, CIBERONC, ES 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0858-914X","authenticated-orcid":false,"given":"Eva","family":"Castellano","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital 12 de Octubre, i+12, CNIO, CIBERONC, ES 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Teixid\u00f3","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedicine, Centro de Investigaciones Biol\u00f3gicas, CSIC, ES 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Mart\u00ednez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital 12 de Octubre, i+12, CNIO, CIBERONC, ES 28041 Madrid, Spain"},{"name":"Medicine Department, Medicine School, Universidad Complutense de Madrid, ES 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17046","DOI":"10.1038\/nrdp.2017.46","article-title":"Multiple myeloma","volume":"3","author":"Kumar","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"156","DOI":"10.3389\/fimmu.2019.00156","article-title":"Molecular Players in Hematologic Tumor Cell Trafficking","volume":"10","author":"Teixido","year":"2019","journal-title":"Front Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1182\/blood-2012-01-379024","article-title":"Myeloma as a model for the process of metastasis: Implications for therapy","volume":"120","author":"Ghobrial","year":"2012","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/imr.12011","article-title":"The establishment of the plasma cell survival niche in the bone marrow","volume":"251","author":"Chu","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41568-020-0245-2","article-title":"Bone marrow niches in haematological malignancies","volume":"20","author":"Bonnet","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrclinonc.2017.197","article-title":"The bone-marrow niche in MDS and MGUS: Implications for AML and MM","volume":"15","author":"Ghobrial","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"788","DOI":"10.3389\/fimmu.2019.00788","article-title":"In the Right Place, at the Right Time: Spatiotemporal Conditions Determining Plasma Cell Survival and Function","volume":"10","author":"Lindquist","year":"2019","journal-title":"Front Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1084\/jem.194.1.45","article-title":"A coordinated change in chemokine responsiveness guides plasma cell movements","volume":"194","author":"Hargreaves","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.immuni.2004.05.001","article-title":"Cellular niches controlling B lymphocyte behavior within bone marrow during development","volume":"20","author":"Tokoyoda","year":"2004","journal-title":"Immunity"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1084\/jem.20041185","article-title":"The role of CXCR4 in maintaining peripheral B cell compartments and humoral immunity","volume":"200","author":"Nie","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/sj.leu.2402717","article-title":"Expression and function of chemokine receptors in human multiple myeloma","volume":"17","author":"Moller","year":"2003","journal-title":"Leukemia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1182\/blood-2006-07-035857","article-title":"Mechanisms of regulation of CXCR4\/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma","volume":"109","author":"Alsayed","year":"2007","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4341","DOI":"10.1182\/blood-2008-10-186668","article-title":"CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy","volume":"113","author":"Azab","year":"2009","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1182\/blood.V97.2.346","article-title":"Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1\/fibronectin and VCAM-1","volume":"97","author":"Hidalgo","year":"2001","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/leu.2015.332","article-title":"In vivo adhesion of malignant B cells to bone marrow microvasculature is regulated by alpha4beta1 cytoplasmic-binding proteins","volume":"30","author":"Leiva","year":"2016","journal-title":"Leukemia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1182\/blood-2002-10-3190","article-title":"Transforming growth factor-beta1 down-regulates expression of chemokine stromal cell-derived factor-1: Functional consequences in cell migration and adhesion","volume":"102","author":"Wright","year":"2003","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6202","DOI":"10.1182\/blood-2010-06-292243","article-title":"Integrin \u03b27-mediated regulation of multiple myeloma cell adhesion, migration, and invasion","volume":"117","author":"Neri","year":"2011","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S1535-6108(04)00019-4","article-title":"Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma","volume":"5","author":"Hurt","year":"2004","journal-title":"Cancer Cell"},{"key":"ref_20","first-page":"2862","article-title":"A unique pathway in the homing of murine multiple myeloma cells: CD44v10 mediates binding to bone marrow endothelium","volume":"61","author":"Asosingh","year":"2001","journal-title":"Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1182\/blood.V91.1.154","article-title":"A novel P-selectin glycoprotein ligand-1 monoclonal antibody recognizes an epitope within the tyrosine sulfate motif of human PSGL-1 and blocks recognition of both P- and L-selectin","volume":"91","author":"Snapp","year":"1998","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1182\/blood-2011-07-368050","article-title":"P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment","volume":"119","author":"Azab","year":"2012","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1182\/blood-2014-03-560862","article-title":"The sialyltransferase ST3GAL6 influences homing and survival in multiple myeloma","volume":"124","author":"Glavey","year":"2014","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3324\/haematol.2018.212266","article-title":"Sialyltransferase inhibition leads to inhibition of tumor cell interactions with E-selectin, VCAM1, and MADCAM1, and improves survival in a human multiple myeloma mouse model","volume":"105","author":"Natoni","year":"2020","journal-title":"Haematologica"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1182\/blood.V84.7.2269.2269","article-title":"Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures","volume":"84","author":"Lokhorst","year":"1994","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1046\/j.1365-2141.1999.01762.x","article-title":"Characterization of VLA-4-dependent myeloma cell adhesion to fibronectin and VCAM-1","volume":"107","author":"Teixido","year":"1999","journal-title":"Br. J. Haematol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1182\/blood.V96.5.1953","article-title":"Cell-cell contact between marrow stromal cells and myeloma cells via VCAM-1 and alpha(4)beta(1)-integrin enhances production of osteoclast-stimulating activity","volume":"96","author":"Michigami","year":"2000","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1111\/j.1365-2141.2011.08864.x","article-title":"The selective adhesion molecule inhibitor Natalizumab decreases multiple myeloma cell growth in the bone marrow microenvironment: Therapeutic implications","volume":"155","author":"Podar","year":"2011","journal-title":"Br. J. Haematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1182\/blood-2004-01-0236","article-title":"Anti-alpha4 integrin antibody suppresses the development of multiple myeloma and associated osteoclastic osteolysis","volume":"104","author":"Mori","year":"2004","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1158\/1535-7163.91.4.1","article-title":"Anti-alpha4 integrin monoclonal antibody inhibits multiple myeloma growth in a murine model","volume":"4","author":"Olson","year":"2005","journal-title":"Mol. Cancer Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1146\/annurev-pathol-011110-130249","article-title":"Pathogenesis of myeloma","volume":"6","author":"Anderson","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1182\/blood-2014-11-568881","article-title":"Pathogenesis beyond the cancer clone(s) in multiple myeloma","volume":"125","author":"Bianchi","year":"2015","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1182\/blood.V93.5.1658","article-title":"Cell adhesion mediated drug resistance (CAM-DR): Role of integrins and resistance to apoptosis in human myeloma cell lines","volume":"93","author":"Damiano","year":"1999","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/onc.2008.385","article-title":"Bortezomib overcomes cell-adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma","volume":"28","author":"Kikuchi","year":"2009","journal-title":"Oncogene"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41375-019-0588-4","article-title":"Transcriptional profiling of circulating tumor cells in multiple myeloma: A new model to understand disease dissemination","volume":"34","author":"Simicek","year":"2020","journal-title":"Leukemia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1038\/leu.2013.148","article-title":"Reduced CXCR4 expression is associated with extramedullary disease in a mouse model of myeloma and predicts poor survival in multiple myeloma patients treated with bortezomib","volume":"27","author":"Stessman","year":"2013","journal-title":"Leukemia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1158\/1541-7786.MCR-10-0288","article-title":"Macrophage migration inhibitory factor is secreted by rhabdomyosarcoma cells, modulates tumor metastasis by binding to CXCR4 and CXCR7 receptors and inhibits recruitment of cancer-associated fibroblasts","volume":"8","author":"Tarnowski","year":"2010","journal-title":"Mol. Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zheng, Y., Wang, Q., Li, T., Qian, J., Lu, Y., Li, Y., Bi, E., Reu, F., Qin, Y., and Drazba, J. (2016). Role of Myeloma-Derived MIF in Myeloma Cell Adhesion to Bone Marrow and Chemotherapy Response. J. Natl. Cancer Inst., 108.","DOI":"10.1093\/jnci\/djw131"},{"key":"ref_39","first-page":"200","article-title":"Clinical significance of chemokine receptor (CCR1, CCR2 and CXCR4) expression in human myeloma cells: The association with disease activity and survival","volume":"91","author":"Leleu","year":"2006","journal-title":"Haematologica"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5452","DOI":"10.1158\/0008-5472.CAN-17-0115","article-title":"HIF-2alpha Promotes Dissemination of Plasma Cells in Multiple Myeloma by Regulating CXCL12\/CXCR4 and CCR1","volume":"77","author":"Vandyke","year":"2017","journal-title":"Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1146\/annurev-pathol-012615-044414","article-title":"Hematopoietic Stem Cell Niche in Health and Disease","volume":"11","author":"Hoggatt","year":"2016","journal-title":"Annu. Rev. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nri.2017.53","article-title":"Adult haematopoietic stem cell niches","volume":"17","author":"Crane","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.immuni.2018.03.024","article-title":"Niches for Hematopoietic Stem Cells and Their Progeny","volume":"48","author":"Wei","year":"2018","journal-title":"Immunity"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.cell.2005.05.026","article-title":"SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells","volume":"121","author":"Kiel","year":"2005","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41580-019-0103-9","article-title":"Haematopoietic stem cell activity and interactions with the niche","volume":"20","author":"Pinho","year":"2019","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1172\/JCI115870","article-title":"Role of beta 1 and beta 2 integrins in the adhesion of human CD34hi stem cells to bone marrow stroma","volume":"90","author":"Hemler","year":"1992","journal-title":"J. Clin. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1182\/blood.V80.2.388.bloodjournal802388","article-title":"Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells","volume":"80","author":"Simmons","year":"1992","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1182\/blood.V92.3.894","article-title":"Role of adhesion molecules in the homing and mobilization of murine hematopoietic stem and progenitor cells","volume":"92","author":"Vermeulen","year":"1998","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1084\/jem.181.5.1805","article-title":"Cytokines increase human hemopoietic cell adhesiveness by activation of very late antigen (VLA)-4 and VLA-5 integrins","volume":"181","author":"Leavesley","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1182\/blood.V95.11.3289","article-title":"The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: Role in transendothelial\/stromal migration and engraftment of NOD\/SCID mice","volume":"95","author":"Peled","year":"2000","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1182\/blood.V90.6.2217","article-title":"CD44 regulates hematopoietic progenitor distribution, granuloma formation, and tumorigenicity","volume":"90","author":"Schmits","year":"1997","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"14423","DOI":"10.1073\/pnas.95.24.14423","article-title":"Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow","volume":"95","author":"Frenette","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1182\/blood-2003-04-1212","article-title":"PSGL-1 participates in E-selectin-mediated progenitor homing to bone marrow: Evidence for cooperation between E-selectin ligands and alpha4 integrin","volume":"102","author":"Katayama","year":"2003","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4689","DOI":"10.1182\/blood-2009-05-220988","article-title":"Canonical BMP signaling is dispensable for hematopoietic stem cell function in both adult and fetal liver hematopoiesis, but essential to preserve colon architecture","volume":"115","author":"Singbrant","year":"2010","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S1074-7613(94)80014-6","article-title":"Interleukin-6 is required in vivo for the regulation of stem cells and committed progenitors of the hematopoietic system","volume":"1","author":"Bernad","year":"1994","journal-title":"Immunity"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1182\/blood-2011-11-393991","article-title":"FGF signaling facilitates postinjury recovery of mouse hematopoietic system","volume":"120","author":"Zhao","year":"2012","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1084\/jem.192.9.1365","article-title":"The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells","volume":"192","author":"Karanu","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1182\/blood.V99.7.2369","article-title":"Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favors lymphoid over myeloid lineage outcome","volume":"99","author":"Stier","year":"2002","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.stem.2008.02.011","article-title":"Canonical notch signaling is dispensable for the maintenance of adult hematopoietic stem cells","volume":"2","author":"Maillard","year":"2008","journal-title":"Cell Stem. Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.cell.2011.09.053","article-title":"Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche","volume":"147","author":"Yamazaki","year":"2011","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.cell.2007.08.025","article-title":"Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment","volume":"131","author":"Sacchetti","year":"2007","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/nature07547","article-title":"Endochondral ossification is required for haematopoietic stem-cell niche formation","volume":"457","author":"Chan","year":"2009","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nature09262","article-title":"Mesenchymal and haematopoietic stem cells form a unique bone marrow niche","volume":"466","author":"Michurina","year":"2010","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.immuni.2010.08.017","article-title":"The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche","volume":"33","author":"Omatsu","year":"2010","journal-title":"Immunity"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1084\/jem.20101688","article-title":"Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche","volume":"208","author":"Chow","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4815","DOI":"10.1182\/blood-2009-11-253534","article-title":"Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs","volume":"116","author":"Winkler","year":"2010","journal-title":"Blood"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1038\/nm.3707","article-title":"Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion","volume":"20","author":"Bruns","year":"2014","journal-title":"Nat. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1038\/nm.3706","article-title":"Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells","volume":"20","author":"Zhao","year":"2014","journal-title":"Nat. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5238","DOI":"10.1182\/blood-2012-10-463414","article-title":"Megakaryocytes promote murine osteoblastic HSC niche expansion and stem cell engraftment after radioablative conditioning","volume":"121","author":"Olson","year":"2013","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nature01874","article-title":"Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL","volume":"425","author":"Staller","year":"2003","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1172\/JCI17669","article-title":"Expansion of human SCID-repopulating cells under hypoxic conditions","volume":"112","author":"Danet","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/nm1075","article-title":"Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1","volume":"10","author":"Ceradini","year":"2004","journal-title":"Nat. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.stem.2010.06.020","article-title":"Regulation of the HIF-1alpha level is essential for hematopoietic stem cells","volume":"7","author":"Takubo","year":"2010","journal-title":"Cell Stem. Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/nature12612","article-title":"Arteriolar niches maintain haematopoietic stem cell quiescence","volume":"502","author":"Kunisaki","year":"2013","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/nm.3155","article-title":"Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration","volume":"19","author":"Lucas","year":"2013","journal-title":"Nat. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/nature06685","article-title":"Haematopoietic stem cell release is regulated by circadian oscillations","volume":"452","author":"Lucas","year":"2008","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1034\/j.1600-065X.2003.00041.x","article-title":"Homing of antibody secreting cells","volume":"194","author":"Cyster","year":"2003","journal-title":"Immunol Rev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/nri3795","article-title":"The generation of antibody-secreting plasma cells","volume":"15","author":"Nutt","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1126\/science.8342023","article-title":"Signal sequence trap: A cloning strategy for secreted proteins and type I membrane proteins","volume":"261","author":"Tashiro","year":"1993","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1073\/pnas.91.6.2305","article-title":"Molecular cloning and structure of a pre-B-cell growth-stimulating factor","volume":"91","author":"Nagasawa","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1084\/jem.184.3.1101","article-title":"A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1)","volume":"184","author":"Bleul","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.4049\/jimmunol.169.3.1277","article-title":"Chemotactic responsiveness toward ligands for CXCR3 and CXCR4 is regulated on plasma blasts during the time course of a memory immune response","volume":"169","author":"Hauser","year":"2002","journal-title":"J. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4273","DOI":"10.1038\/ncomms5273","article-title":"Shp1 signalling is required to establish the long-lived bone marrow plasma cell pool","volume":"5","author":"Li","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.4049\/jimmunol.169.8.4213","article-title":"The role of bone marrow-derived stromal cells in the maintenance of plasma cell longevity","volume":"169","author":"Underhill","year":"2002","journal-title":"J. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"361","DOI":"10.4049\/jimmunol.180.1.361","article-title":"Maintenance of long-lived plasma cells and serological memory despite mature and memory B cell depletion during CD20 immunotherapy in mice","volume":"180","author":"DiLillo","year":"2008","journal-title":"J. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1002\/eji.201344313","article-title":"Static and dynamic components synergize to form a stable survival niche for bone marrow plasma cells","volume":"44","author":"Zehentmeier","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"10241","DOI":"10.1016\/S0021-9258(18)99215-X","article-title":"Functional evidence for three distinct and independently inhibitable adhesion activities mediated by the human integrin VLA-4. Correlation with distinct alpha 4 epitopes","volume":"266","author":"Pulido","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3698","DOI":"10.1038\/s41467-018-05853-7","article-title":"Factors of the bone marrow microniche that support human plasma cell survival and immunoglobulin secretion","volume":"9","author":"Nguyen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/j.cell.2019.04.040","article-title":"A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia","volume":"177","author":"Baryawno","year":"2019","journal-title":"Cell"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1182\/blood.V85.2.487.487","article-title":"Differentiation of early plasma cells on bone marrow stromal cells requires interleukin-6 for escaping from apoptosis","volume":"85","author":"Kawano","year":"1995","journal-title":"Blood"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/ni.1981","article-title":"Eosinophils are required for the maintenance of plasma cells in the bone marrow","volume":"12","author":"Chu","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1002\/eji.201747227","article-title":"Eosinophils are not essential for maintenance of murine plasma cells in the bone marrow","volume":"48","author":"Haberland","year":"2018","journal-title":"Eur. J. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1002\/eji.201747229","article-title":"No strict requirement for eosinophils for bone marrow plasma cell survival","volume":"48","author":"Bortnick","year":"2018","journal-title":"Eur. J. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1182\/blood-2009-12-259457","article-title":"Megakaryocytes constitute a functional component of a plasma cell niche in the bone marrow","volume":"116","author":"Winter","year":"2010","journal-title":"Blood"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.4049\/jimmunol.180.6.3655","article-title":"Cutting edge: The dependence of plasma cells and independence of memory B cells on BAFF and APRIL","volume":"180","author":"Benson","year":"2008","journal-title":"J. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.cell.2007.05.014","article-title":"A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency","volume":"129","author":"Walkley","year":"2007","journal-title":"Cell"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/nature20131","article-title":"Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment","volume":"539","author":"Dong","year":"2016","journal-title":"Nature"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.devcel.2019.04.011","article-title":"Exosome-Mediated Metastasis: Communication from a Distance","volume":"49","author":"Wortzel","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/nri855","article-title":"Exosomes: Composition, biogenesis and function","volume":"2","author":"Zitvogel","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41556-018-0250-9","article-title":"Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication","volume":"21","author":"Mathieu","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1172\/JCI66517","article-title":"BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression","volume":"123","author":"Roccaro","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1182\/blood-2014-03-562439","article-title":"Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells","volume":"124","author":"Wang","year":"2014","journal-title":"Blood"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"13772","DOI":"10.18632\/oncotarget.3830","article-title":"Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation","volume":"6","author":"Raimondi","year":"2015","journal-title":"Oncotarget"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3748","DOI":"10.1182\/blood-2014-05-576116","article-title":"Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1","volume":"124","author":"Umezu","year":"2014","journal-title":"Blood"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1126\/science.1164390","article-title":"Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells","volume":"322","author":"Colmone","year":"2008","journal-title":"Science"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1084\/jem.20140131","article-title":"Niche displacement of human leukemic stem cells uniquely allows their competitive replacement with healthy HSPCs","volume":"211","author":"Boyd","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/s41467-017-02376-5","article-title":"Proliferation dynamics of acute myeloid leukaemia and haematopoietic progenitors competing for bone marrow space","volume":"9","author":"Akinduro","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3456","DOI":"10.1172\/JCI61188","article-title":"Molecular pathogenesis of multiple myeloma and its premalignant precursor","volume":"122","author":"Kuehl","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3992","DOI":"10.1182\/blood-2006-05-026112","article-title":"Multiple myeloma bone disease: Pathophysiology of osteoblast inhibition","volume":"108","author":"Giuliani","year":"2006","journal-title":"Blood"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1158\/1078-0432.CCR-10-1804","article-title":"Advances in the biology and treatment of bone disease in multiple myeloma","volume":"17","author":"Raje","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nrc3910","article-title":"Metastasis prevention by targeting the dormant niche","volume":"15","author":"Ghajar","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1182\/blood-2013-07-517136","article-title":"Osteoblastic niche supports the growth of quiescent multiple myeloma cells","volume":"123","author":"Chen","year":"2014","journal-title":"Blood"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1182\/blood.2018880930","article-title":"A niche-dependent myeloid transcriptome signature defines dormant myeloma cells","volume":"134","author":"Khoo","year":"2019","journal-title":"Blood"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"8983","DOI":"10.1038\/ncomms9983","article-title":"Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche","volume":"6","author":"Lawson","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.bone.2010.06.016","article-title":"Osteoblast function in myeloma","volume":"48","author":"Roodman","year":"2011","journal-title":"Bone"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1056\/NEJMoa030847","article-title":"The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma","volume":"349","author":"Tian","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1359\/jbmr.081104","article-title":"Inhibiting Dickkopf-1 (Dkk1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma","volume":"24","author":"Heath","year":"2009","journal-title":"J. Bone Miner. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/s41375-019-0404-1","article-title":"Aberrant Wnt signaling in multiple myeloma: Molecular mechanisms and targeting options","volume":"33","author":"Kocemba","year":"2019","journal-title":"Leukemia"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/leu.2012.190","article-title":"Myeloma cells inhibit non-canonical wnt co-receptor ror2 expression in human bone marrow osteoprogenitor cells: Effect of wnt5a\/ror2 pathway activation on the osteogenic differentiation impairment induced by myeloma cells","volume":"27","author":"Bolzoni","year":"2013","journal-title":"Leukemia"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41375-019-0486-9","article-title":"The WNT receptor ROR2 drives the interaction of multiple myeloma cells with the microenvironment through AKT activation","volume":"34","author":"Frenquelli","year":"2020","journal-title":"Leukemia"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1038\/leu.2013.27","article-title":"Anti-Notch treatment prevents multiple myeloma cells localization to the bone marrow via the chemokine system CXCR4\/SDF-1","volume":"27","author":"Mirandola","year":"2013","journal-title":"Leukemia"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3511","DOI":"10.1182\/blood-2003-07-2254","article-title":"Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells","volume":"103","author":"Jundt","year":"2004","journal-title":"Blood"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1182\/blood-2003-12-4114","article-title":"Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines","volume":"104","author":"Houde","year":"2004","journal-title":"Blood"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1182\/blood-2004-12-4986","article-title":"Myeloma cells block RUNX2\/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation","volume":"106","author":"Giuliani","year":"2005","journal-title":"Blood"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1038\/leu.2009.65","article-title":"Mesenchymal stem cells from multiple myeloma patients display distinct genomic profile as compared with those from normal donors","volume":"23","author":"Garayoa","year":"2009","journal-title":"Leukemia"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/sj.leu.2404621","article-title":"Bone marrow mesenchymal stem cells are abnormal in multiple myeloma","volume":"21","author":"Corre","year":"2007","journal-title":"Leukemia"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/imr.12233","article-title":"Targeting the bone marrow microenvironment in multiple myeloma","volume":"263","author":"Kawano","year":"2015","journal-title":"Immunol. Rev."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1038\/sj.leu.2402295","article-title":"Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: Therapeutic applications","volume":"15","author":"Gupta","year":"2001","journal-title":"Leukemia"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1182\/blood-2013-08-524025","article-title":"Growth differentiating factor 15 enhances the tumor-initiating and self-renewal potential of multiple myeloma cells","volume":"123","author":"Tanno","year":"2014","journal-title":"Blood"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Nakamura, K., Smyth, M.J., and Martinet, L. (2020). Cancer immunoediting and immune dysregulation in multiple myeloma. Blood.","DOI":"10.1182\/blood.2020006540"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1182\/blood-2016-05-636357","article-title":"The immunotherapy era of myeloma: Monoclonal antibodies, vaccines, and adoptive T-cell therapies","volume":"128","author":"Hoyos","year":"2016","journal-title":"Blood"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1158\/1078-0432.CCR-19-2111","article-title":"How to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma","volume":"26","author":"Cohen","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1038\/s41375-018-0061-9","article-title":"Mesenchymal stem cells in multiple myeloma: A therapeutical tool or target?","volume":"32","author":"Xu","year":"2018","journal-title":"Leukemia"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1097\/CCO.0000000000000615","article-title":"The microenvironment in myeloma","volume":"32","author":"Lomas","year":"2020","journal-title":"Curr. Opin. Oncol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"3625","DOI":"10.1182\/blood-2009-05-220285","article-title":"Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug-induced apoptosis","volume":"114","author":"Zheng","year":"2009","journal-title":"Blood"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s12307-019-00232-2","article-title":"Tumor-Infiltrating Immunosuppressive Cells in Cancer-Cell Plasticity, Tumor Progression and Therapy Response","volume":"12","year":"2019","journal-title":"Cancer Microenviron"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Petty, A.J., and Yang, Y. (2019). Tumor-Associated Macrophages in Hematologic Malignancies: New Insights and Targeted Therapies. Cells, 8.","DOI":"10.3390\/cells8121526"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"11283","DOI":"10.18632\/oncotarget.2207","article-title":"Multiple myeloma cells recruit tumor-supportive macrophages through the CXCR4\/CXCL12 axis and promote their polarization toward the M2 phenotype","volume":"5","author":"Beider","year":"2014","journal-title":"Oncotarget"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/bjh.16158","article-title":"JAK1\/2 pathway inhibition suppresses M2 polarization and overcomes resistance of myeloma to lenalidomide by reducing TRIB1, MUC1, CD44, CXCL12, and CXCR4 expression","volume":"188","author":"Chen","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"24218","DOI":"10.18632\/oncotarget.4523","article-title":"Chemokines CCL2, 3, 14 stimulate macrophage bone marrow homing, proliferation, and polarization in multiple myeloma","volume":"6","author":"Li","year":"2015","journal-title":"Oncotarget"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/path.4860","article-title":"Tumour-associated macrophage-mediated survival of myeloma cells through STAT3 activation","volume":"241","author":"Maes","year":"2017","journal-title":"J. Pathol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/leu.2017.193","article-title":"Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma","volume":"32","author":"Wang","year":"2018","journal-title":"Leukemia"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"112685","DOI":"10.18632\/oncotarget.22340","article-title":"Prognostic value of diametrically polarized tumor-associated macrophages in multiple myeloma","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.7150\/jca.30102","article-title":"High numbers of CD163+ tumor-associated macrophages correlate with poor prognosis in multiple myeloma patients receiving bortezomib-based regimens","volume":"10","author":"Wang","year":"2019","journal-title":"J. Cancer"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1038\/leu.2015.191","article-title":"Tumor-associated macrophages and extracellular matrix metalloproteinase inducer in prognosis of multiple myeloma","volume":"30","author":"Panchabhai","year":"2016","journal-title":"Leukemia"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.leukres.2015.06.003","article-title":"The novel biomarker of alternative macrophage activation, soluble mannose receptor (sMR\/sCD206): Implications in multiple myeloma","volume":"39","author":"Andersen","year":"2015","journal-title":"Leuk. Res."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Wang, Q., Zhao, D., Xian, M., Wang, Z., Bi, E., Su, P., Qian, J., Ma, X., Yang, M., and Liu, L. (2020). MIF as a biomarker and therapeutic target for overcoming resistance to proteasome inhibitors in human myeloma. Blood.","DOI":"10.1182\/blood.2020005795"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/s41419-019-2012-4","article-title":"CCL2 promotes macrophages-associated chemoresistance via MCPIP1 dual catalytic activities in multiple myeloma","volume":"10","author":"Xu","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/j.1365-2141.2012.09154.x","article-title":"Macrophages and mesenchymal stromal cells support survival and proliferation of multiple myeloma cells","volume":"158","author":"Kim","year":"2012","journal-title":"Br. J. Haematol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/leu.2012.272","article-title":"PSGL-1\/selectin and ICAM-1\/CD18 interactions are involved in macrophage-induced drug resistance in myeloma","volume":"27","author":"Zheng","year":"2013","journal-title":"Leukemia"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/path.4723","article-title":"Bortezomib-induced pro-inflammatory macrophages as a potential factor limiting anti-tumour efficacy","volume":"239","author":"Magidey","year":"2016","journal-title":"J. Pathol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1182\/blood-2018-01-825240","article-title":"Myeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade","volume":"132","author":"Minnie","year":"2018","journal-title":"Blood"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.neo.2019.05.006","article-title":"Clodronate-Liposome Mediated Macrophage Depletion Abrogates Multiple Myeloma Tumor Establishment In Vivo","volume":"21","author":"Opperman","year":"2019","journal-title":"Neoplasia"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/sj.onc.1210691","article-title":"Vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma","volume":"27","author":"Scavelli","year":"2008","journal-title":"Oncogene"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/s12253-015-9921-z","article-title":"Interleukin-10 Induces Both Plasma Cell Proliferation and Angiogenesis in Multiple Myeloma","volume":"21","author":"Alexandrakis","year":"2015","journal-title":"Pathol. Oncol. Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"183602","DOI":"10.1155\/2013\/183602","article-title":"Multiple myeloma macrophages: Pivotal players in the tumor microenvironment","volume":"2013","author":"Berardi","year":"2013","journal-title":"J. Oncol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1007\/s00262-019-02374-0","article-title":"CD4(+) T cells indirectly kill tumor cells via induction of cytotoxic macrophages in mouse models","volume":"68","author":"Bogen","year":"2019","journal-title":"Cancer Immunol. Immunother"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1182\/bloodadvances.2020001434","article-title":"CD4+ T-cell killing of multiple myeloma cells is mediated by resident bone marrow macrophages","volume":"4","author":"Haabeth","year":"2020","journal-title":"Blood Adv."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.3389\/fimmu.2018.01684","article-title":"Tumor Killing by CD4+ T Cells Is Mediated via Induction of Inducible Nitric Oxide Synthase-Dependent Macrophage Cytotoxicity","volume":"9","author":"Fauskanger","year":"2018","journal-title":"Front Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/ncomms1239","article-title":"Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer","volume":"2","author":"Haabeth","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.1158\/0008-5472.CAN-14-3640","article-title":"Tumors Escape CD4+ T-cell-Mediated Immunosurveillance by Impairing the Ability of Infiltrating Macrophages to Indirectly Present Tumor Antigens","volume":"75","author":"Tveita","year":"2015","journal-title":"Cancer Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1002\/eji.201444659","article-title":"Indirect CD4+ T-cell-mediated elimination of MHC II(NEG) tumor cells is spatially restricted and fails to prevent escape of antigen-negative cells","volume":"44","author":"Tveita","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1182\/blood-2016-01-695395","article-title":"Evaluation of the potential therapeutic benefits of macrophage reprogramming in multiple myeloma","volume":"128","author":"Samaniego","year":"2016","journal-title":"Blood"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1007\/s00262-016-1861-2","article-title":"Circulating immune cell phenotype can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory\/relapsed multiple myeloma","volume":"65","author":"Lee","year":"2016","journal-title":"Cancer Immunol. Immunother"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"85764","DOI":"10.18632\/oncotarget.7969","article-title":"Granulocyte-like myeloid derived suppressor cells (G-MDSC) are increased in multiple myeloma and are driven by dysfunctional mesenchymal stem cells (MSC)","volume":"7","author":"Giallongo","year":"2016","journal-title":"Oncotarget"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.3109\/10428194.2014.904511","article-title":"Myeloid derived suppressor cells are numerically, functionally and phenotypically different in patients with multiple myeloma","volume":"55","author":"Favaloro","year":"2014","journal-title":"Leuk. Lymphoma"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s41375-018-0242-6","article-title":"APRIL signaling via TACI mediates immunosuppression by T regulatory cells in multiple myeloma: Therapeutic implications","volume":"33","author":"Tai","year":"2019","journal-title":"Leukemia"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1080\/14737159.2018.1470929","article-title":"PMN-MDSC and arginase are increased in myeloma and may contribute to resistance to therapy","volume":"18","author":"Romano","year":"2018","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00262-014-1646-4","article-title":"Tumor-induced CD14+HLA-DR (-\/low) myeloid-derived suppressor cells correlate with tumor progression and outcome of therapy in multiple myeloma patients","volume":"64","author":"Wang","year":"2015","journal-title":"Cancer Immunol. Immunother"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Kuwahara-Ota, S., Shimura, Y., Steinebach, C., Isa, R., Yamaguchi, J., Nishiyama, D., Fujibayashi, Y., Takimoto-Shimomura, T., Mizuno, Y., and Matsumura-Kimoto, Y. (2020). Lenalidomide and pomalidomide potently interfere with induction of myeloid-derived suppressor cells in multiple myeloma. Br. J. Haematol.","DOI":"10.1111\/bjh.16881"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"4607","DOI":"10.1158\/1078-0432.CCR-15-0200","article-title":"Lenalidomide Enhances Immune Checkpoint Blockade-Induced Immune Response in Multiple Myeloma","volume":"21","author":"Gorgun","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"10532","DOI":"10.18632\/oncotarget.3300","article-title":"Multiple myeloma induces Mcl-1 expression and survival of myeloid-derived suppressor cells","volume":"6","author":"Lub","year":"2015","journal-title":"Oncotarget"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s00432-018-2790-6","article-title":"Decitabine shows potent anti-myeloma activity by depleting monocytic myeloid-derived suppressor cells in the myeloma microenvironment","volume":"145","author":"Zhou","year":"2019","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/path.4712","article-title":"Multiple myeloma exosomes establish a favourable bone marrow microenvironment with enhanced angiogenesis and immunosuppression","volume":"239","author":"Wang","year":"2016","journal-title":"J. Pathol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"43992","DOI":"10.18632\/oncotarget.6083","article-title":"The bone marrow microenvironment enhances multiple myeloma progression by exosome-mediated activation of myeloid-derived suppressor cells","volume":"6","author":"Wang","year":"2015","journal-title":"Oncotarget"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1182\/blood-2015-01-623975","article-title":"Dendritic cells accumulate in the bone marrow of myeloma patients where they protect tumor plasma cells from CD8+ T-cell killing","volume":"126","author":"Leone","year":"2015","journal-title":"Blood"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1038\/leu.2017.135","article-title":"A novel agent SL-401 induces anti-myeloma activity by targeting plasmacytoid dendritic cells, osteoclastogenesis and cancer stem-like cells","volume":"31","author":"Ray","year":"2017","journal-title":"Leukemia"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"e1444411","DOI":"10.1080\/2162402X.2018.1444411","article-title":"Quantitative and functional alterations of 6-sulfo LacNac dendritic cells in multiple myeloma","volume":"7","author":"Lamarthee","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"5705","DOI":"10.1038\/s41598-018-23943-w","article-title":"Compromised functionality of monocyte-derived dendritic cells in multiple myeloma patients may limit their use in cancer immunotherapy","volume":"8","author":"Shinde","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1038\/s41598-020-58859-x","article-title":"High-density neutrophils in MGUS and multiple myeloma are dysfunctional and immune-suppressive due to increased STAT3 downstream signaling","volume":"10","author":"Romano","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Puglisi, F., Parrinello, N.L., Giallongo, C., Cambria, D., Camiolo, G., Bellofiore, C., Conticello, C., Del Fabro, V., Leotta, V., and Markovic, U. (2019). Plasticity of High-Density Neutrophils in Multiple Myeloma is Associated with Increased Autophagy Via STAT3. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143548"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1182\/blood.2019004537","article-title":"Immunogenomic identification and characterization of granulocytic myeloid-derived suppressor cells in multiple myeloma","volume":"136","author":"Perez","year":"2020","journal-title":"Blood"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Wong, T.W., Kita, H., Hanson, C.A., Walters, D.K., Arendt, B.K., and Jelinek, D.F. (2013). Induction of malignant plasma cell proliferation by eosinophils. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070554"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1016\/j.celrep.2017.01.067","article-title":"T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow","volume":"18","author":"Konradt","year":"2017","journal-title":"Cell Rep."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1159\/000443275","article-title":"The Impact of Mast Cell Density on the Progression of Bone Disease in Multiple Myeloma Patients","volume":"168","author":"Vyzoukaki","year":"2015","journal-title":"Int. Arch Allergy Immunol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1158\/1078-0432.CCR-17-2003","article-title":"Platelets Enhance Multiple Myeloma Progression via IL-1beta Upregulation","volume":"24","author":"Takagi","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"5385","DOI":"10.1182\/blood-2009-10-246660","article-title":"Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma","volume":"115","author":"Prabhala","year":"2010","journal-title":"Blood"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"e148","DOI":"10.1038\/bcj.2013.34","article-title":"Long-term survival in multiple myeloma is associated with a distinct immunological profile, which includes proliferative cytotoxic T-cell clones and a favourable Treg\/Th17 balance","volume":"3","author":"Bryant","year":"2013","journal-title":"Blood Cancer J."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1080\/10428194.2019.1579324","article-title":"Evaluating the role of Tregs in the progression of multiple myeloma","volume":"60","author":"Lad","year":"2019","journal-title":"Leuk. Lymphoma"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1158\/1078-0432.CCR-19-1714","article-title":"Marrow-Infiltrating Regulatory T Cells Correlate with the Presence of Dysfunctional CD4+PD-1+ Cells and Inferior Survival in Patients with Newly Diagnosed Multiple Myeloma","volume":"26","author":"Alrasheed","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/bjc.2011.575","article-title":"The frequency of T regulatory cells modulates the survival of multiple myeloma patients: Detailed characterisation of immune status in multiple myeloma","volume":"106","author":"Giannopoulos","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s12935-018-0687-8","article-title":"Increased activated regulatory T cell subsets and aging Treg-like cells in multiple myeloma and monoclonal gammopathy of undetermined significance: A case control study","volume":"18","author":"Wang","year":"2018","journal-title":"Cancer Cell Int."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1172\/JCI88169","article-title":"Blocking IFNAR1 inhibits multiple myeloma-driven Treg expansion and immunosuppression","volume":"128","author":"Kawano","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1186\/1479-5876-10-247","article-title":"Indoleamine 2,3-dioxygenase 1 (IDO1) activity correlates with immune system abnormalities in multiple myeloma","volume":"10","author":"Bonanno","year":"2012","journal-title":"J. Transl. Med."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1182\/blood-2015-12-687749","article-title":"Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma","volume":"128","author":"Krejcik","year":"2016","journal-title":"Blood"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/CJI.0b013e31821ca6ce","article-title":"PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell\/myeloma fusion vaccine","volume":"34","author":"Rosenblatt","year":"2011","journal-title":"J. Immunother"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"e285","DOI":"10.1038\/bcj.2015.7","article-title":"Immunomodulatory molecule PD-L1 is expressed on malignant plasma cells and myeloma-propagating pre-plasma cells in the bone marrow of multiple myeloma patients","volume":"5","author":"Yousef","year":"2015","journal-title":"Blood Cancer J."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"12641","DOI":"10.1038\/s41598-020-69616-5","article-title":"PD-L1 expression in bone marrow plasma cells as a biomarker to predict multiple myeloma prognosis: Developing a nomogram-based prognostic model","volume":"10","author":"Lee","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"e448","DOI":"10.1016\/S2352-3026(19)30109-7","article-title":"Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): A randomised, open-label, phase 3 trial","volume":"6","author":"Usmani","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"e459","DOI":"10.1016\/S2352-3026(19)30110-3","article-title":"Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): A randomised, open-label, phase 3 trial","volume":"6","author":"Mateos","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1038\/leu.2016.84","article-title":"Multiple myeloma causes clonal T-cell immunosenescence: Identification of potential novel targets for promoting tumour immunity and implications for checkpoint blockade","volume":"30","author":"Suen","year":"2016","journal-title":"Leukemia"},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Bailur, J.K., McCachren, S.S., Doxie, D.B., Shrestha, M., Pendleton, K., Nooka, A.K., Neparidze, N., Parker, T.L., Bar, N., and Kaufman, J.L. (2019). Early alterations in stem-like\/resident T cells, innate and myeloid cells in the bone marrow in preneoplastic gammopathy. JCI Insight, 5.","DOI":"10.1172\/jci.insight.127807"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13045-016-0345-3","article-title":"T cells in multiple myeloma display features of exhaustion and senescence at the tumor site","volume":"9","author":"Thangavadivel","year":"2016","journal-title":"J. Hematol. Oncol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"4493","DOI":"10.1182\/blood-2012-05-429415","article-title":"Tumor cells in multiple myeloma patients inhibit myeloma-reactive T cells through carcinoembryonic antigen-related cell adhesion molecule-6","volume":"121","author":"Hose","year":"2013","journal-title":"Blood"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.1182\/blood-2002-04-1121","article-title":"Human myeloma cells stimulate the receptor activator of nuclear factor-kappa B ligand (RANKL) in T lymphocytes: A potential role in multiple myeloma bone disease","volume":"100","author":"Giuliani","year":"2002","journal-title":"Blood"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1182\/blood-2005-03-1080","article-title":"IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma","volume":"106","author":"Ehrlich","year":"2005","journal-title":"Blood"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1182\/blood-2005-07-2719","article-title":"Interleukin-3 (IL-3) is overexpressed by T lymphocytes in multiple myeloma patients","volume":"107","author":"Giuliani","year":"2006","journal-title":"Blood"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"3554","DOI":"10.1182\/blood-2010-05-283895","article-title":"A novel role of IL-17-producing lymphocytes in mediating lytic bone disease in multiple myeloma","volume":"116","author":"Noonan","year":"2010","journal-title":"Blood"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1080\/10428190500472503","article-title":"Immune parameters in multiple myeloma patients: Influence of treatment and correlation with opportunistic infections","volume":"47","author":"Brandhorst","year":"2006","journal-title":"Leuk. Lymphoma"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1046\/j.1365-2141.1996.4651006.x","article-title":"Analysis of natural killer-associated antigens in peripheral blood and bone marrow of multiple myeloma patients and prognostic implications","volume":"93","author":"Moro","year":"1996","journal-title":"Br. J. Haematol."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1007\/s12032-007-0007-y","article-title":"Clinical stage-depending decrease of NK cell activity in multiple myeloma patients","volume":"24","author":"Jurisic","year":"2007","journal-title":"Med. Oncol."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/BF02827242","article-title":"IgG M-components in active myeloma patients induce a down-regulation of natural killer cell activity","volume":"27","author":"Frassanito","year":"1997","journal-title":"Int. J. Clin. Lab Res."},{"key":"ref_213","doi-asserted-by":"crossref","unstructured":"Konjevi\u0107, G., Vuleti\u0107, A., Mirja\u010di\u0107 Martinovi\u0107, K., Colovi\u0107, N., \u010colovi\u0107, M., and Juri\u0161i\u0107, V. (2016). Decreased CD161 activating and increased CD158a inhibitory receptor expression on NK cells underlies impaired NK cell cytotoxicity in patients with multiple myeloma. J. Clin. Pathol.","DOI":"10.1136\/jclinpath-2016-203614"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/sj.leu.2404096","article-title":"Impaired activating receptor expression pattern in natural killer cells from patients with multiple myeloma","volume":"20","author":"Fauriat","year":"2006","journal-title":"Leukemia"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1073\/pnas.0711293105","article-title":"MHC class I chain-related protein A antibodies and shedding are associated with the progression of multiple myeloma","volume":"105","author":"Jinushi","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"8444","DOI":"10.1158\/0008-5472.CAN-06-4230","article-title":"The requirement for DNAM-1, NKG2D, and NKp46 in the natural killer cell-mediated killing of myeloma cells","volume":"67","author":"Meade","year":"2007","journal-title":"Cancer Res."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"4766","DOI":"10.1158\/0008-5472.CAN-15-1320","article-title":"Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer Cells by Altering the Chemokine Microenvironment","volume":"75","author":"Ponzetta","year":"2015","journal-title":"Cancer Res."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1084\/jem.20021650","article-title":"A reversible defect in natural killer T cell function characterizes the progression of premalignant to malignant multiple myeloma","volume":"197","author":"Dhodapkar","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"694","DOI":"10.2119\/molmed.2016.00198","article-title":"Adenosine Generated in the Bone Marrow Niche Through a CD38-Mediated Pathway Correlates with Progression of Human Myeloma","volume":"22","author":"Horenstein","year":"2016","journal-title":"Mol. Med."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.4049\/jimmunol.174.2.1073","article-title":"A2A adenosine receptor induction inhibits IFN-gamma production in murine CD4+ T cells","volume":"174","author":"Lappas","year":"2005","journal-title":"J. Immunol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1158\/0008-5472.CAN-10-4246","article-title":"CD73-deficient mice have increased antitumor immunity and are resistant to experimental metastasis","volume":"71","author":"Stagg","year":"2011","journal-title":"Cancer Res."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1158\/0008-5472.CAN-17-2826","article-title":"A2AR Adenosine Signaling Suppresses Natural Killer Cell Maturation in the Tumor Microenvironment","volume":"78","author":"Young","year":"2018","journal-title":"Cancer Res."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1182\/blood-2007-03-081646","article-title":"A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells","volume":"111","author":"Zarek","year":"2008","journal-title":"Blood"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"760","DOI":"10.3389\/fimmu.2019.00760","article-title":"CD38 in Adenosinergic Pathways and Metabolic Re-programming in Human Multiple Myeloma Cells: In-tandem Insights From Basic Science to Therapy","volume":"10","author":"Horenstein","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"e26246","DOI":"10.4161\/onci.26246","article-title":"A CD38\/CD203a\/CD73 ectoenzymatic pathway independent of CD39 drives a novel adenosinergic loop in human T lymphocytes","volume":"2","author":"Horenstein","year":"2013","journal-title":"Oncoimmunology"},{"key":"ref_226","doi-asserted-by":"crossref","unstructured":"Yang, R., Elsaadi, S., Misund, K., Abdollahi, P., Vandsemb, E.N., Moen, S.H., Kusnierczyk, A., Slupphaug, G., Standal, T., and Waage, A. (2020). Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade. J. Immunother Cancer, 8.","DOI":"10.1136\/jitc-2020-000610"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.clim.2006.11.007","article-title":"Soluble MICA as an independent prognostic factor for the overall survival and progression-free survival of multiple myeloma patients","volume":"123","author":"Rebmann","year":"2007","journal-title":"Clin. Immunol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/nature01112","article-title":"Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation","volume":"419","author":"Groh","year":"2002","journal-title":"Nature"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/2\/217\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:09:00Z","timestamp":1760159340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/2\/217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,9]]},"references-count":228,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["cancers13020217"],"URL":"https:\/\/doi.org\/10.3390\/cancers13020217","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,9]]}}}