{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:45:41Z","timestamp":1790703941042,"version":"4.1.0"},"reference-count":155,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005189","name":"Leukemia and Lymphoma Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Multiple myeloma (MM), a malignant neoplasm of plasma cells that reside in the bone marrow (BM), is universally preceded by a precursor state termed monoclonal gammopathy of undetermined significance (MGUS). Many individuals with MGUS never progress to MM or progress over many years. Therefore, MGUS provides a unique opportunity to surveil changes in the BM tumor microenvironment throughout disease progression. It is increasingly appreciated that MGUS cells carry many of the genetic changes found in MM. Prior studies have also shown that MGUS cells can be recognized by the immune system, leading to early changes in the BM immune environment compared to that of healthy individuals, including alterations in both innate and adaptive immunity. Progression to clinical MM is associated with attrition of T cells with stem memory-like features and instead accumulation of T cells with more terminally differentiated features. Recent clinical studies have suggested that early application of immune-modulatory drugs, which are known to activate both innate and adaptive immunity, can delay the progression to clinical MM. Understanding the biology of how the immune response and tumors coevolve over time is needed to develop novel immune-based approaches to achieve durable and effective prevention of clinical malignancy.<\/jats:p>","DOI":"10.3389\/fimmu.2021.632564","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T05:39:07Z","timestamp":1614317947000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Co-evolution of Immune Response in Multiple Myeloma: Implications for Immune Prevention"],"prefix":"10.3389","volume":"12","author":[{"given":"Samuel S.","family":"McCachren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita M.","family":"Dhodapkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhav V.","family":"Dhodapkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","first-page":"2599","DOI":"10.1182\/blood-2016-09-692954","article-title":"MGUS to myeloma: a mysterious gammopathy of underexplored significance","volume":"128","author":"Dhodapkar","year":"2016","journal-title":"Blood."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1038\/s41467-020-15740-9","article-title":"Timing the initiation of multiple myeloma","volume":"11","author":"Rustad","year":"2020","journal-title":"Nat Commun."},{"key":"B4","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1126\/science.aay2859","article-title":"Cancer cell evolution through the ages","volume":"365","author":"Maley","year":"2019","journal-title":"Science."},{"key":"B5","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1158\/1078-0432.CCR-20-1395","article-title":"Designing evolutionary based interception strategies to block the transition from precursor phases to multiple myeloma","volume":"27","author":"Maura","year":"2020","journal-title":"Clin Cancer Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1111\/bjh.14649","article-title":"Cutting edge genomics reveal new insights into tumour development, disease progression and therapeutic impacts in multiple myeloma","volume":"178","author":"Dutta","year":"2017","journal-title":"Brit J Haematol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1182\/blood.V100.4.1417.h81602001417_1417_1424","article-title":"Genomic abnormalities in monoclonal gammopathy of undetermined significance","volume":"100","author":"Fonseca","year":"2002","journal-title":"Blood."},{"key":"B8","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/nrclinonc.2016.122","article-title":"Genomic complexity of multiple myeloma and its clinical implications","volume":"14","author":"Manier","year":"2017","journal-title":"Nat Rev Clin Oncol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/nrc.2017.63","article-title":"Evolutionary biology of high-risk multiple myeloma","volume":"17","author":"Pawlyn","year":"2017","journal-title":"Nat Rev Cancer."},{"key":"B10","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/leu.2013.199","article-title":"Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms","volume":"28","author":"Walker","year":"2014","journal-title":"Leukemia."},{"key":"B11","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1182\/blood-2012-06-430645","article-title":"Darwinian evolution and tiding clones in multiple myeloma","volume":"120","author":"Bahlis","year":"2012","journal-title":"Blood."},{"key":"B12","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.ccr.2013.12.015","article-title":"Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy","volume":"25","author":"Lohr","year":"2014","journal-title":"Cancer cell."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1038\/ncomms3997","article-title":"Heterogeneity of genomic evolution and mutational profiles in multiple myeloma","volume":"5","author":"Bolli","year":"2014","journal-title":"Nat Commun."},{"key":"B14","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nrc3257","article-title":"The genetic architecture of multiple myeloma","volume":"12","author":"Morgan","year":"2012","journal-title":"Nat Rev Cancer."},{"key":"B15","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1182\/blood-2010-04-279539","article-title":"Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma","volume":"117","author":"Walker","year":"2011","journal-title":"Blood."},{"key":"B16","doi-asserted-by":"publisher","first-page":"3145","DOI":"10.1182\/blood-2007-06-092122","article-title":"The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressor","volume":"111","author":"Marango","year":"2008","journal-title":"Blood."},{"key":"B17","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/nature09837","article-title":"Initial genome sequencing and analysis of multiple myeloma","volume":"471","author":"Chapman","year":"2011","journal-title":"Nature."},{"key":"B18","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1038\/ng.349","article-title":"Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer","volume":"41","author":"van Haaften","year":"2009","journal-title":"Nat Gen."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1038\/s41375-019-0689-0","article-title":"Role of AID in the temporal pattern of acquisition of driver mutations in multiple myeloma","volume":"34","author":"Maura","year":"2020","journal-title":"Leukemia."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2302","DOI":"10.1182\/blood-2011-08-376236","article-title":"Dendritic cell-mediated activation-induced cytidine deaminase (AID)-dependent induction of genomic instability in human myeloma","volume":"119","author":"Koduru","year":"2012","journal-title":"Blood."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1182\/blood.V99.5.1745","article-title":"Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells","volume":"99","author":"Zhan","year":"2002","journal-title":"Blood."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.1158\/0008-5472.CAN-17-3115","article-title":"From MGUS to multiple myeloma, a paradigm for clonal evolution of premalignant cells","volume":"78","author":"van Nieuwenhuijzen","year":"2018","journal-title":"Cancer Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1038\/leu.2014.59","article-title":"Serial exome analysis of disease progression in premalignant gammopathies","volume":"28","author":"Zhao","year":"2014","journal-title":"Leukemia."},{"key":"B24","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41375-018-0206-x","article-title":"Subclonal evolution in disease progression from MGUS\/SMM to multiple myeloma is characterised by clonal stability","volume":"33","author":"Dutta","year":"2019","journal-title":"Leukemia."},{"key":"B25","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1146\/annurev-immunol-031210-101324","article-title":"Natural innate and adaptive immunity to cancer","volume":"29","author":"Vesely","year":"2011","journal-title":"Annu Rev Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2077","DOI":"10.1172\/JCI77181","article-title":"Immunosurveillance and therapy of multiple myeloma are CD226 dependent","volume":"125","author":"Guillerey","year":"2015","journal-title":"J Clin Invest."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1038\/nm.4202","article-title":"Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice","volume":"22","author":"Das","year":"2016","journal-title":"Nat Med."},{"key":"B28","doi-asserted-by":"publisher","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":"B29","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.1182\/blood-2015-03-632919","article-title":"Prospective analysis of antigen-specific immunity, stem-cell antigens, and immune checkpoints in monoclonal gammopathy","volume":"126","author":"Dhodapkar","year":"2015","journal-title":"Blood."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.1002\/eji.1830270919","article-title":"T cell repertoire in patients with multiple myeloma and monoclonal gammopathy of undetermined significance: clonal CD8+ T cell expansions are found preferentially in patients with a low tumor burden","volume":"27","author":"Halapi","year":"1997","journal-title":"Euro J Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1046\/j.1365-2141.2000.02131.x","article-title":"T-cell expansions in patients with multiple myeloma have a phenotype of cytotoxic T cells","volume":"110","author":"Raitakari","year":"2000","journal-title":"Brit J Haematol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.3109\/10428190903216804","article-title":"Prognostically significant cytotoxic T cell clones are stimulated after thalidomide therapy in patients with multiple myeloma","volume":"50","author":"Brown","year":"2009","journal-title":"Leuk Lymphoma."},{"key":"B33","doi-asserted-by":"publisher","first-page":"3939","DOI":"10.1182\/blood-2004-09-3707","article-title":"NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses","volume":"105","author":"van Rhee","year":"2005","journal-title":"Blood."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.1084\/jem.20031030","article-title":"Vigorous premalignancy-specific effector T cell response in the bone marrow of patients with monoclonal gammopathy","volume":"198","author":"Dhodapkar","year":"2003","journal-title":"J Exp Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1182\/blood-2004-04-1422","article-title":"HLA class I, NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells","volume":"105","author":"Carbone","year":"2005","journal-title":"Blood."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e306","DOI":"10.1038\/bcj.2015.32","article-title":"The cellular immune system in myelomagenesis: NK cells and T cells in the development of myeloma [corrected] and their uses in immunotherapies","volume":"5","author":"Dosani","year":"2015","journal-title":"Blood Cancer J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"7502","DOI":"10.1158\/0008-5472.CAN-05-0731","article-title":"MICA expressed by multiple myeloma and monoclonal gammopathy of undetermined significance plasma cells Costimulates pamidronate-activated gammadelta lymphocytes","volume":"65","author":"Girlanda","year":"2005","journal-title":"Cancer Res."},{"key":"B38","doi-asserted-by":"publisher","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":"Zelle-Rieser","year":"2016","journal-title":"J Hematol Oncol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3362","DOI":"10.1182\/blood-2008-04-149393","article-title":"Differential pattern of CD4+ and CD8+ T-cell immunity to MAGE-A1\/A2\/A3 in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma","volume":"112","author":"Goodyear","year":"2008","journal-title":"Blood."},{"key":"B40","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1084\/jem.20062387","article-title":"Frequent and specific immunity to the embryonal stem cell\u2013associated antigen SOX2 in patients with monoclonal gammopathy","volume":"204","author":"Spisek","year":"2007","journal-title":"J Experi Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"3276","DOI":"10.1182\/blood-2009-04-219436","article-title":"Identification of novel antigens with induced immune response in monoclonal gammopathy of undetermined significance","volume":"114","author":"Blotta","year":"2009","journal-title":"Blood."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e127807","DOI":"10.1172\/jci.insight.127807","article-title":"Early alterations in stem-like\/resident T cells, innate and myeloid cells in the bone marrow in preneoplastic gammopathy","volume":"5","author":"Bailur","year":"2019","journal-title":"JCI insight."},{"key":"B43","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s43018-020-0053-3","article-title":"Single-cell RNA sequencing reveals compromised immune microenvironment in precursor stages of multiple myeloma","volume":"1","author":"Zavidij","year":"2020","journal-title":"Nat Cancer."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1002\/cncr.21746","article-title":"Characterization of bone marrow T cells in monoclonal gammopathy of undetermined significance, multiple myeloma, and plasma cell leukemia demonstrates increased infiltration by cytotoxic\/Th1 T cells demonstrating a squed TCR-Vbeta repertoire","volume":"106","author":"P\u00e9rez-Andres","year":"2006","journal-title":"Cancer."},{"key":"B45","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/BF00199953","article-title":"Surface markers and cytotoxic activities of lymphocytes in monoclonal gammopathy of undetermined significance and untreated multiple myeloma. Increased phytohemagglutinin-induced cellular cytotoxicity and inverted helper\/suppressor cell ratio are features common to both diseases","volume":"25","author":"De Rossi","year":"1987","journal-title":"Cancer Immunol Immunotherapy."},{"key":"B46","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1111\/j.1600-0609.1990.tb00443.x","article-title":"Natural killer cell activity in monoclonal gammopathies: relation to disease activity","volume":"45","author":"Osterborg","year":"1990","journal-title":"Euro J Haematol."},{"key":"B47","doi-asserted-by":"publisher","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":"B48","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1111\/imm.12082","article-title":"Differential expression of natural killer cell activating receptors in blood versus bone marrow in patients with monoclonal gammopathy","volume":"139","author":"Costello","year":"2013","journal-title":"Immunology."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2286","DOI":"10.1182\/blood-2010-02-271874","article-title":"The PD-1\/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody","volume":"116","author":"Benson","year":"2010","journal-title":"Blood."},{"key":"B50","doi-asserted-by":"publisher","first-page":"263","DOI":"10.3324\/haematol.2014.117531","article-title":"Daratumumab-mediated lysis of primary multiple myeloma cells is enhanced in combination with the human anti-KIR antibody IPH2102 and lenalidomide","volume":"100","author":"Inger","year":"2015","journal-title":"Haematologica."},{"key":"B51","doi-asserted-by":"publisher","first-page":"4055","DOI":"10.1158\/1078-0432.CCR-15-0304","article-title":"A phase I trial of the Anti-KIR antibody IPH2101 and lenalidomide in patients with relapsed\/refractory multiple myeloma","volume":"21","author":"Benson","year":"2015","journal-title":"Clin Cancer Res."},{"key":"B52","doi-asserted-by":"publisher","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 Experi Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1111\/cei.12196","article-title":"Natural killer T cell defects in multiple myeloma and the impact of lenalidomide therapy","volume":"175","author":"Chan","year":"2014","journal-title":"Clin Exp Immunol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1182\/blood-2005-10-4184","article-title":"Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications","volume":"108","author":"Chang","year":"2006","journal-title":"Blood."},{"key":"B55","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1182\/blood-2012-06-435503","article-title":"Clinical regressions and broad immune activation following combination therapy targeting human NKT cells in myeloma","volume":"121","author":"Richter","year":"2013","journal-title":"Blood."},{"key":"B56","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1038\/ni.3482","article-title":"NK cells and type 1 innate lymphoid cells: partners in host defense","volume":"17","author":"Spits","year":"2016","journal-title":"Nat Immunol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1038\/ni.3489","article-title":"Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis","volume":"17","author":"Klose","year":"2016","journal-title":"Nat Immunol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"2343","DOI":"10.1182\/bloodadvances.2017012732","article-title":"Changes in bone marrow innate lymphoid cell subsets in monoclonal gammopathy: target for IMiD therapy","volume":"1","author":"Kini Bailur","year":"2017","journal-title":"Blood Adv."},{"key":"B59","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.immuni.2014.09.021","article-title":"Tumor-associated macrophages: from mechanisms to therapy","volume":"41","author":"Noy","year":"2014","journal-title":"Immunity."},{"key":"B60","doi-asserted-by":"publisher","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":"B61","doi-asserted-by":"publisher","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":"B62","doi-asserted-by":"publisher","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":"B63","doi-asserted-by":"publisher","first-page":"3064","DOI":"10.1182\/blood.V93.9.3064.409k07_3064_3073","article-title":"Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma","volume":"93","author":"Vacca","year":"1999","journal-title":"Blood."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1016\/j.exphem.2009.09.004","article-title":"Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages","volume":"37","author":"Kim","year":"2009","journal-title":"Experi Hematol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.blre.2016.04.002","article-title":"Myeloid-derived suppressor cells: the green light for myeloma immune escape","volume":"30","author":"Malek","year":"2016","journal-title":"Blood Rev."},{"key":"B66","doi-asserted-by":"publisher","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":"Leukemia Lymphoma."},{"key":"B67","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1111\/j.1365-3083.2010.02463.x","article-title":"Increased level of both CD4+FOXP3+ regulatory T cells and CD14+HLA-DR\u2013\/low myeloid-derived suppressor cells and decreased level of dendritic cells in patients with multiple myeloma","volume":"72","author":"Brimnes","year":"2010","journal-title":"Scand J Immunol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"3815","DOI":"10.4049\/jimmunol.1203373","article-title":"Myeloid-derived suppressor cells regulate growth of multiple myeloma by inhibiting T cells in bone marrow","volume":"190","author":"Ramachandran","year":"2013","journal-title":"J Immunol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1016\/j.ccell.2018.02.007","article-title":"Dysregulated IL-18 Is a key driver of immunosuppression and a possible therapeutic target in the multiple myeloma microenvironment","volume":"33","author":"Nakamura","year":"2018","journal-title":"Cancer Cell."},{"key":"B70","doi-asserted-by":"publisher","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":"B71","doi-asserted-by":"publisher","first-page":"36","DOI":"10.7150\/jca.5046","article-title":"Dendritic cells in the cancer microenvironment","volume":"4","author":"Ma","year":"2013","journal-title":"J Cancer."},{"key":"B72","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1097\/PAP.0b013e3181bb6bc2","article-title":"Plasmacytoid dendritic cells: physiologic roles and pathologic states","volume":"16","author":"Jegalian","year":"2009","journal-title":"Adv Anatomic Pathol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"2655","DOI":"10.1182\/blood-2006-03-011353","article-title":"Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after DC injection of cytokine matured DCs in myeloma patients","volume":"108","author":"Banerjee","year":"2006","journal-title":"Blood."},{"key":"B74","doi-asserted-by":"publisher","first-page":"2878","DOI":"10.1182\/blood-2008-03-143222","article-title":"Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma","volume":"112","author":"Dhodapkar","year":"2008","journal-title":"Blood."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1084\/jem.20052136","article-title":"Enhancement of clonogenicity of human multiple myeloma by dendritic cells","volume":"203","author":"Kukreja","year":"2006","journal-title":"J Exp Med."},{"key":"B76","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.ccr.2009.08.019","article-title":"Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target","volume":"16","author":"Chauhan","year":"2009","journal-title":"Cancer Cell."},{"key":"B77","doi-asserted-by":"publisher","first-page":"15055","DOI":"10.1074\/jbc.RA117.000633","article-title":"The contribution of cross-talk between the cell-surface proteins CD36 and CD47-TSP-1 in osteoclast formation and function","volume":"293","author":"Koduru","year":"2018","journal-title":"J Biol Chem."},{"key":"B78","doi-asserted-by":"publisher","first-page":"3413","DOI":"10.1182\/blood-2009-03-211920","article-title":"Dominant role of CD47-thrombospondin-1 interactions in myeloma-induced fusion of human dendritic cells: implications for bone disease","volume":"114","author":"Kukreja","year":"2009","journal-title":"Blood."},{"key":"B79","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.exphem.2011.04.006","article-title":"Immature dendritic cells from patients with multiple myeloma are prone to osteoclast differentiation in vitro","volume":"39","author":"Tucci","year":"2011","journal-title":"Experi Hematol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"13009","DOI":"10.1073\/pnas.202491499","article-title":"T cells from the tumor microenvironment of patients with progressive myeloma can generate strong, tumor-specific cytolytic responses to autologous, tumor-loaded dendritic cells","volume":"99","author":"Dhodapkar","year":"2002","journal-title":"Proc Natl Acad Sci USA."},{"key":"B81","doi-asserted-by":"publisher","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":"B82","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1146\/annurev-med-012017-043208","article-title":"CD8 T cell exhaustion in chronic infection and cancer: opportunities for interventions","volume":"69","author":"Hashimoto","year":"2018","journal-title":"Annu Rev Med."},{"key":"B83","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1158\/2326-6066.CIR-15-0055","article-title":"T-cell exhaustion in multiple myeloma relapse after autotransplant: optimal timing of immunotherapy","volume":"4","author":"Chung","year":"2016","journal-title":"Cancer Immunol Res."},{"key":"B84","doi-asserted-by":"publisher","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":"B85","doi-asserted-by":"publisher","first-page":"32024","DOI":"10.18632\/oncotarget.25882","article-title":"PD1 is expressed on exhausted T cells as well as virus specific memory CD8+ T cells in the bone marrow of myeloma patients","volume":"9","author":"Sponaas","year":"2018","journal-title":"Oncotarget."},{"key":"B86","doi-asserted-by":"publisher","first-page":"101415","DOI":"10.1016\/j.smim.2020.101415","article-title":"Tissue-resident memory-like T cells in tumor immunity: clinical implications","volume":"2020","author":"Dhodapkar","year":"2020","journal-title":"Semin Immunol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"2817","DOI":"10.1182\/blood.V98.9.2817","article-title":"Clonal cytotoxic T cells are expanded in myeloma and reside in the CD8(+)CD57(+)CD28(-) compartment","volume":"98","author":"Sze","year":"2001","journal-title":"Blood."},{"key":"B88","doi-asserted-by":"publisher","first-page":"4593","DOI":"10.1182\/bloodadvances.2020002237","article-title":"Inverse relationship between oligoclonal expanded CD69- TTE and CD69+ TTE cells in bone marrow of multiple myeloma patients","volume":"4","author":"Vuckovic","year":"2020","journal-title":"Blood Adv."},{"key":"B89","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1038\/leu.2015.104","article-title":"The failure of immune checkpoint blockade in multiple myeloma with PD-1 inhibitors in a phase 1 study","volume":"29","author":"Suen","year":"2015","journal-title":"Leukemia."},{"key":"B90","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.3389\/fimmu.2018.02204","article-title":"Checkpoint inhibition in myeloma: opportunities and challenges","volume":"9","author":"Costa","year":"2018","journal-title":"Front Immunol."},{"key":"B91","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s40425-017-0256-z","article-title":"Adoptive cell therapy using PD-1+ myeloma-reactive T cells eliminates established myeloma in mice","volume":"5","author":"Jing","year":"2017","journal-title":"J ImmunoTher Cancer."},{"key":"B92","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1182\/blood-2006-10-051482","article-title":"Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-{gamma} and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway","volume":"110","author":"Liu","year":"2007","journal-title":"Blood."},{"key":"B93","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/leu.2012.213","article-title":"Marrow stromal cells induce B7-H1 expression on myeloma cells, generating aggressive characteristics in multiple myeloma","volume":"27","author":"Tamura","year":"2013","journal-title":"Leukemia."},{"key":"B94","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1038\/leu.2015.79","article-title":"PD-L1\/PD-1 presence in the tumor microenvironment and activity of PD-1 blockade in multiple myeloma","volume":"29","author":"Paiva","year":"2015","journal-title":"Leukemia."},{"key":"B95","doi-asserted-by":"publisher","first-page":"924","DOI":"10.3390\/cancers12040924","article-title":"PD-L1-PD-1 pathway in the pathophysiology of multiple myeloma","volume":"12","author":"Tamura","year":"2020","journal-title":"Cancers."},{"key":"B96","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/s41408-019-0234-4","article-title":"Mass cytometry dissects T cell heterogeneity in the immune tumor microenvironment of common dysproteinemias at diagnosis and after first line therapies","volume":"9","author":"Kourelis","year":"2019","journal-title":"Blood Cancer J."},{"key":"B97","doi-asserted-by":"publisher","first-page":"e129353","DOI":"10.1172\/jci.insight.129353","article-title":"Differential effects of PD-L1 versus PD-1 blockade on myeloid inflammation in human cancer","volume":"5","author":"Bar","year":"2020","journal-title":"JCI Insight."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1182\/blood-2018-01-825265","article-title":"TIGIT immune checkpoint blockade restores CD8(+) T cell immunity against multiple myeloma","volume":"132","author":"Guillerey","year":"2018","journal-title":"Blood."},{"key":"B99","doi-asserted-by":"publisher","first-page":"e000610","DOI":"10.1136\/jitc-2020-000610","article-title":"Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade","volume":"8","author":"Yang","year":"2020","journal-title":"J Immunotherapy Cancer."},{"key":"B100","doi-asserted-by":"publisher","first-page":"3940","DOI":"10.1182\/blood-2005-09-3671","article-title":"In vivo peripheral expansion of naive CD4+CD25highFoxP3+ regulatory T cells in patients with multiple myeloma","volume":"107","author":"Beyer","year":"2006","journal-title":"Blood."},{"key":"B101","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1182\/blood-2005-08-3101","article-title":"Dysfunctional T regulatory cells in multiple myeloma","volume":"107","author":"Prabhala","year":"2006","journal-title":"Blood."},{"key":"B102","doi-asserted-by":"publisher","first-page":"e35981","DOI":"10.1371\/journal.pone.0035981","article-title":"Tumour cell generation of inducible regulatory T-cells in multiple myeloma is contact-dependent and antigen-presenting cell-independent","volume":"7","author":"Feyler","year":"2012","journal-title":"PLoS ONE."},{"key":"B103","doi-asserted-by":"publisher","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":"B104","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1002\/eji.201847659","article-title":"Targeting Treg cells in cancer immunotherapy","volume":"49","author":"Tanaka","year":"2019","journal-title":"Eur J Immunol"},{"key":"B105","doi-asserted-by":"publisher","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":"B106","doi-asserted-by":"publisher","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":"B107","doi-asserted-by":"publisher","first-page":"e1093278","DOI":"10.1080\/2162402X.2015.1093278","article-title":"Non-redundant roles for Th17 and Th22 cells in multiple myeloma clinical correlates","volume":"5","author":"Di Lullo","year":"2016","journal-title":"OncoImmunology."},{"key":"B108","doi-asserted-by":"publisher","first-page":"4832","DOI":"10.1038\/s41467-018-07305-8","article-title":"Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression","volume":"9","author":"Calcinotto","year":"2018","journal-title":"Nat Commun."},{"key":"B109","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1172\/JCI98888","article-title":"Bone marrow transplantation generates T cell-dependent control of myeloma in mice","volume":"129","author":"Vuckovic","year":"2019","journal-title":"J Clin Invest."},{"key":"B110","doi-asserted-by":"publisher","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":"B111","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/s41409-019-0681-3","article-title":"Combined immune score of lymphocyte to monocyte ratio and immunoglobulin levels predicts treatment-free survival of multiple myeloma patients after autologous stem cell transplant","volume":"55","author":"Sweiss","year":"2020","journal-title":"Bone Marrow Transplant."},{"key":"B112","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1172\/JCI85113","article-title":"Human regulatory B cells in health and disease: therapeutic potential","volume":"127","author":"Mauri","year":"2017","journal-title":"J Clin Investig."},{"key":"B113","doi-asserted-by":"publisher","first-page":"e547","DOI":"10.1038\/bcj.2017.24","article-title":"Regulatory B cell-myeloma cell interaction confers immunosuppression and promotes their survival in the bone marrow milieu","volume":"7","author":"Zhang","year":"2017","journal-title":"Blood Cancer J."},{"key":"B114","doi-asserted-by":"publisher","first-page":"4615","DOI":"10.1182\/blood-2002-04-1121","article-title":"Human myeloma cells stimulate the receptor activator of nuclear factor-\u03baB ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease","volume":"100","author":"Giuliani","year":"2002","journal-title":"Blood."},{"key":"B115","doi-asserted-by":"publisher","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":"B116","doi-asserted-by":"publisher","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":"B117","doi-asserted-by":"publisher","first-page":"2308","DOI":"10.1182\/blood-2003-06-1992","article-title":"IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells","volume":"103","author":"Lee","year":"2004","journal-title":"Blood."},{"key":"B118","doi-asserted-by":"publisher","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":"B119","doi-asserted-by":"publisher","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":"B120","doi-asserted-by":"publisher","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":"B121","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.blre.2013.08.002","article-title":"Dickkopf-1 is a key regulator of myeloma bone disease: opportunities and challenges for therapeutic intervention","volume":"27","author":"Zhou","year":"2013","journal-title":"Blood Rev."},{"key":"B122","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1111\/bjh.15026","article-title":"Bone marrow Dikkopf-1 levels are a new independent risk factor for progression in patients with smouldering myeloma","volume":"183","author":"Dalla Palma","year":"2018","journal-title":"Br J Haematol"},{"key":"B123","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/j.bone.2007.12.006","article-title":"Dkk1-induced inhibition of Wnt signaling in osteoblast differentiation is an underlying mechanism of bone loss in multiple myeloma","volume":"42","author":"Qiang","year":"2008","journal-title":"Bone."},{"key":"B124","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1517\/14728220903025770","article-title":"Dickkopf-1: a suitable target for the management of myeloma bone disease","volume":"13","author":"Gavriatopoulou","year":"2009","journal-title":"Expert Opin Therap Targets."},{"key":"B125","doi-asserted-by":"publisher","first-page":"954","DOI":"10.3389\/fimmu.2017.00954","article-title":"Emerging roles of osteoclasts in the modulation of bone microenvironment and immune suppression in multiple myeloma","volume":"8","author":"Mansour","year":"2017","journal-title":"Front Immunol."},{"key":"B126","doi-asserted-by":"publisher","first-page":"5477","DOI":"10.4049\/jimmunol.0803897","article-title":"Cross-presentation by osteoclasts induces FoxP3 in CD8+ T cells","volume":"182","author":"Kiesel","year":"2009","journal-title":"J Immunol."},{"key":"B127","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1002\/jbmr.2868","article-title":"Inflammatory osteoclasts prime TNF\u03b1-producing CD4(+) T cells and express CX(3) CR1","volume":"31","author":"Ib\u00e1\u00f1ez","year":"2016","journal-title":"J Bone Mineral Res."},{"key":"B128","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1182\/blood.V128.22.3303.3303","article-title":"Osteoclasts promote immune suppressive microenvironment in multiple myeloma: therapeutic implication","volume":"128","author":"An","year":"2016","journal-title":"Blood."},{"key":"B129","doi-asserted-by":"publisher","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":"B130","doi-asserted-by":"publisher","first-page":"381","DOI":"10.3324\/haematol.2016.145060","article-title":"Due to interleukin-6 type cytokine redundancy only glycoprotein 130 receptor blockade efficiently inhibits myeloma growth","volume":"102","author":"Renate","year":"2017","journal-title":"Haematologica."},{"key":"B131","doi-asserted-by":"publisher","first-page":"2440","DOI":"10.1002\/cncr.11072","article-title":"A review of the cytokine network in multiple myeloma","volume":"97","author":"Lauta","year":"2003","journal-title":"Cancer"},{"key":"B132","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.1002\/(SICI)1097-0142(19980515)82:10&lt;1860::AID-CNCR7&gt;3.0.CO;2-R","article-title":"The prognostic value of soluble interleukin-6 receptor in patients with multiple myeloma","volume":"82","author":"Stasi","year":"1998","journal-title":"Cancer."},{"key":"B133","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1046\/j.1365-2141.1996.4721018.x","article-title":"Soluble interleukin-6 receptor (sIL-6R), a new prognostic factor in multiple myeloma","volume":"93","author":"Kyrtsonis","year":"1996","journal-title":"Brit J Haematol."},{"key":"B134","doi-asserted-by":"publisher","first-page":"2695","DOI":"10.1038\/s41375-019-0470-4","article-title":"Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells","volume":"33","author":"Mishra","year":"2019","journal-title":"Leukemia."},{"key":"B135","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1038\/s41375-019-0493-x","article-title":"Targeting histone deacetylase 3 (HDAC3) in the bone marrow microenvironment inhibits multiple myeloma proliferation by modulating exosomes and IL-6 trans-signaling","volume":"34","author":"Ho","year":"2020","journal-title":"Leukemia."},{"key":"B136","doi-asserted-by":"publisher","first-page":"3772","DOI":"10.1158\/1078-0432.CCR-18-3470","article-title":"Randomized, double-blind, placebo-controlled, multicenter study of siltuximab in high-risk smoldering multiple myeloma","volume":"25","author":"Brighton","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B137","doi-asserted-by":"publisher","first-page":"5814","DOI":"10.1158\/1078-0432.CCR-20-2119","article-title":"Race-dependent differences in risk, genomics, and Epstein-Barr virus exposure in monoclonal gammopathies: results of SWOG S0120","volume":"26","author":"Dhodapkar","year":"2020","journal-title":"Clin Cancer Res."},{"key":"B138","doi-asserted-by":"publisher","first-page":"e140179","DOI":"10.1172\/jci.insight.140179","article-title":"Risk associated alterations in marrow T cells in pediatric leukemia","volume":"5","author":"Bailur","year":"2020","journal-title":"JCI Insight."},{"key":"B139","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1016\/j.hoc.2007.08.003","article-title":"Mouse models of human myeloma","volume":"21","author":"Mitsiades","year":"2007","journal-title":"Hematol Oncol Clin North Am."},{"key":"B140","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1056\/NEJMoa1508808","article-title":"Clonal immunoglobulin against lysolipids in the origin of myeloma","volume":"374","author":"Nair","year":"2016","journal-title":"N Engl J Med."},{"key":"B141","doi-asserted-by":"publisher","first-page":"e98259","DOI":"10.1172\/jci.insight.98259","article-title":"Antigen-mediated regulation in monoclonal gammopathies and myeloma","volume":"3","author":"Nair","year":"2018","journal-title":"JCI Insight."},{"key":"B142","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.ymgme.2020.01.009","article-title":"Glucosylsphingosine but not Saposin C, is the target antigen in Gaucher disease-associated gammopathy","volume":"129","author":"Nair","year":"2020","journal-title":"Mol Genet Metab."},{"key":"B143","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1182\/blood.V90.5.1960","article-title":"Myeloma bone marrow plasma cells: evidence for their capacity as antigen-presenting cells","volume":"90","author":"Yi","year":"1997","journal-title":"Blood."},{"key":"B144","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1038\/sj.leu.2403647","article-title":"Clonal plasma cells from monoclonal gammopathy of undetermined significance, multiple myeloma and plasma cell leukemia show different expression profiles of molecules involved in the interaction with the immunological bone marrow microenvironment","volume":"19","author":"P\u00e9rez-Andr\u00e9s","year":"2005","journal-title":"Leukemia."},{"key":"B145","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1182\/blood-2009-06-228676","article-title":"Alterations in the antigen processing-presenting machinery of transformed plasma cells are associated with reduced recognition by CD8+ T cells and characterize the progression of MGUS to multiple myeloma","volume":"115","author":"Racanelli","year":"2010","journal-title":"Blood."},{"key":"B146","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/nrc.2017.69","article-title":"Classifying the evolutionary and ecological features of neoplasms","volume":"17","author":"Maley","year":"2017","journal-title":"Nat Rev Cancer."},{"key":"B147","doi-asserted-by":"publisher","first-page":"2397","DOI":"10.1001\/jama.2010.1713","article-title":"Multiple myeloma precursor disease","volume":"304","author":"Landgren","year":"2010","journal-title":"JAMA."},{"key":"B148","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.hoc.2014.06.005","article-title":"Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma","volume":"28","author":"Kyle","year":"2014","journal-title":"Hematol Oncol Clin North Am."},{"key":"B149","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1111\/j.1600-0609.1993.tb00148.x","article-title":"Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I\u2013a randomized study. Myeloma Group of Western Sweden","volume":"50","author":"Hjorth","year":"1993","journal-title":"Euro J Haematol."},{"key":"B150","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1054\/bjoc.1999.1087","article-title":"Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Cooperative group of study and treatment of multiple myeloma","volume":"82","author":"Riccardi","year":"2000","journal-title":"Brit J Cancer."},{"key":"B151","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/sj.leu.2402866","article-title":"Thalidomide as initial therapy for early-stage myeloma","volume":"17","author":"Rajkumar","year":"2003","journal-title":"Leukemia."},{"key":"B152","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1056\/NEJMoa1300439","article-title":"Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma","volume":"369","author":"Mateos","year":"2013","journal-title":"N Engl J Med"},{"key":"B153","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1200\/JCO.19.01740","article-title":"Randomized trial of lenalidomide versus observation in smoldering multiple myeloma","volume":"38","author":"Lonial","year":"2020","journal-title":"J Clin Oncol."},{"key":"B154","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1200\/EDBK_278915","article-title":"The role of early intervention in high-risk smoldering myeloma","volume":"40","author":"Joseph","year":"2020","journal-title":"Am Soc Clin Oncol Educ Book."},{"key":"B155","doi-asserted-by":"publisher","first-page":"2385","DOI":"10.3389\/fimmu.2019.02385","article-title":"Moving immunoprevention beyond virally mediated malignancies: do we need to link it to early detection?","volume":"10","author":"Dhodapkar","year":"2019","journal-title":"Front Immunol."}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.632564\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T05:39:10Z","timestamp":1614317950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.632564\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,26]]},"references-count":155,"alternative-id":["10.3389\/fimmu.2021.632564"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.632564","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,26]]},"article-number":"632564"}}