{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:59:36Z","timestamp":1790762376666,"version":"4.1.0"},"reference-count":146,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Follicular Lymphoma (FL), the most common indolent non-Hodgkin\u2019s B cell lymphoma, is a paradigm of the immune microenvironment\u2019s contribution to disease onset, progression, and heterogeneity. Over the last few years, state-of-the-art technologies, including whole-exome sequencing, single-cell RNA sequencing, and mass cytometry, have precisely dissected the specific cellular phenotypes present in the FL microenvironment network and their role in the disease. In this already complex picture, the presence of recurring mutations, including KMT2D, CREBBP, EZH2, and TNFRSF14, have a prominent contributory role, with some of them finely tuning this exquisite dependence of FL on its microenvironment. This precise characterization of the enemy (FL) and its allies (microenvironment) has paved the way for the development of novel therapies aimed at dismantling this contact network, weakening tumor cell support, and reactivating the host\u2019s immune response against the tumor. In this review, we will describe the main microenvironment actors, together with the current and future therapeutic approaches targeting them.<\/jats:p>","DOI":"10.3390\/cancers13040641","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T08:33:48Z","timestamp":1612514028000},"page":"641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Follicular Lymphoma Microenvironment: An Intricate Network Ready for Therapeutic Intervention"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9248-9883","authenticated-orcid":false,"given":"C\u00e8lia","family":"Doba\u00f1o-L\u00f3pez","sequence":"first","affiliation":[{"name":"Department of Hematology-Oncology, Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7288-7737","authenticated-orcid":false,"given":"Ferran","family":"Araujo-Ayala","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4970-8451","authenticated-orcid":false,"given":"Neus","family":"Serrat","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3193-9099","authenticated-orcid":false,"given":"Juan G.","family":"Valero","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red-Oncolog\u00eda (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3895-5024","authenticated-orcid":false,"given":"Patricia","family":"P\u00e9rez-Gal\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, Institut d\u2019Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red-Oncolog\u00eda (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1182\/asheducation-2017.1.358","article-title":"Follicular lymphoma: Are we ready for a risk-adapted approach?","volume":"2017","author":"Kahl","year":"2017","journal-title":"Hematology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/nrc.2017.127","article-title":"From genetics to the clinic: A translational perspective on follicular lymphoma","volume":"18","author":"Huet","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1182\/blood-2015-11-624288","article-title":"Follicular lymphoma: Evolving therapeutic strategies","volume":"127","author":"Kahl","year":"2018","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4673","DOI":"10.1038\/onc.2014.403","article-title":"The tumor microenvironment shapes hallmarks of mature B-cell malignancies","volume":"34","author":"Shain","year":"2015","journal-title":"Oncogene"},{"key":"ref_5","first-page":"810","article-title":"The tumor microenvironment in follicular lymphoma","volume":"10","author":"Yang","year":"2012","journal-title":"Clin. Adv. Hematol. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Verdi\u00e8re, L., and Fr\u00e9d\u00e9ric Mourcin, K.T. (2018). Microenvironment signaling driving lymphomagenesis. Curr. Opin. Hematol., 335\u2013345.","DOI":"10.1097\/MOH.0000000000000440"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.beha.2011.02.007","article-title":"The microenvironment in follicular lymphoma","volume":"24","author":"Hemato","year":"2011","journal-title":"Best Pract. Res. Clin. Haematol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dave, S.S., Wright, G., Tan, B., Rosenwald, A., Gascoyne, R.D., Chan, W.C., Fisher, R.I., Braziel, R.M., Rimsza, L.M., and Grogan, T.M. (2004). Prediction of Survival in Follicular Lymphoma Based on Molecular Features of Tumor-Infiltrating Immune Cells. N. Engl. J. Med., 2159\u20132169.","DOI":"10.1056\/NEJMoa041869"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chraa, D., Naim, A., Olive, D., and Badou, A. (2019). T lymphocyte subsets in cancer immunity: Friends or foes. J. Leukoc. Biol., 243\u2013255.","DOI":"10.1002\/JLB.MR0318-097R"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.semcancer.2013.08.001","article-title":"The yin and the yang of follicular lymphoma cell niches: Role of microenvironment heterogeneity and plasticity","volume":"24","author":"Tarte","year":"2014","journal-title":"Semin. Cancer Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3458","DOI":"10.1158\/1078-0432.CCR-14-0154","article-title":"Disruption of follicular dendritic cells-follicular lymphoma cross-talk by the pan-PI3K inhibitor BKM120 (buparlisib)","volume":"20","author":"Rodriguez","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1365-2567.2004.02075.x","article-title":"How do follicular dendritic cells interact intimately with B cells in the germinal centre?","volume":"114","author":"Park","year":"2005","journal-title":"Immunology"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Am\u00e9-Thomas, P., Le Priol, J., Yssel, H., Caron, G., Pangault, C., Jean, R., Martin, N., Marafioti, T., Gaulard, P., and Lamy, T. (2011). Characterization of intratumoral follicular helper T cells in follicular lymphoma: Role in the survival of malignant B cells. Leukemia, 1053\u20131063.","DOI":"10.1038\/leu.2011.301"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1038\/leu.2010.223","article-title":"Follicular lymphoma cell niche: Identification of a preeminent IL-4-dependent TFH\u2013B cell axis","volume":"24","author":"Pangault","year":"2010","journal-title":"Leukemia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1182\/blood-2005-08-3376","article-title":"Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma","volume":"107","author":"Yang","year":"2006","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1038\/s41590-019-0515-x","article-title":"Fibroblastic reticular cells enhance T cell metabolism and survival via epigenetic remodeling","volume":"20","author":"Brown","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_17","first-page":"1","article-title":"Fibroblastic Reticular Cells: Organization and Regulation of the T Lymphocyte Life Cycle","volume":"23","author":"Brown","year":"2015","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1182\/blood-2016-08-737239","article-title":"IL-4\/CXCL12 loop is a key regulator of lymphoid stroma function in follicular lymphoma","volume":"129","author":"Pandey","year":"2017","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.imlet.2019.02.005","article-title":"Impact of B cell\/lymphoid stromal cell crosstalk in B-cell physiology and malignancy","volume":"215","author":"Lamaison","year":"2019","journal-title":"Immunol. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1182\/blood-2006-05-020800","article-title":"Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: Role of stromal cells in follicular lymphoma pathogenesis","volume":"109","author":"Monvoisin","year":"2007","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1182\/blood-2011-08-370908","article-title":"Mesenchymal stromal cells orchestrate follicular lymphoma cell niche through the CCL2-dependent recruitment and polarization of monocytes","volume":"119","author":"Guilloton","year":"2012","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/hon.108_2629","article-title":"Deciphering the contribution of macrophages to follicular lymphoma pathogenesis: New insights into therapy","volume":"37","author":"Valero","year":"2019","journal-title":"Hematol. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1182\/blood-2015-04-640912","article-title":"DC-SIGN-expressing macrophages trigger activation of mannosylated IgM B-cell receptor in follicular lymphoma","volume":"126","author":"Amin","year":"2015","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2017.00912","article-title":"Altered N-linked glycosylation in follicular lymphoma and chronic lymphocytic leukemia: Involvement in pathogenesis and potential therapeutic targeting","volume":"8","author":"Hollander","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1182\/blood-2015-04-640805","article-title":"Lectin binding to surface Ig variable regions provides a universal persistent activating signal for follicular lymphoma cells","volume":"126","author":"Linley","year":"2015","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/leu.2011.179","article-title":"Monocytes and T cells cooperate to favor normal and follicular lymphoma B-cell growth: Role of IL-15 and CD40L signaling","volume":"26","author":"Epron","year":"2012","journal-title":"Leukemia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1078\/0344-0338-00421","article-title":"Disappearance of CD21-positive follicular dendritic cells preceding the transformation of follicular lymphoma: Immunohistological study of the transformation using CD21, p53, Ki-67, and P-glycoprotein","volume":"199","author":"Shiozawa","year":"2003","journal-title":"Pathol. Res. Pract."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1200\/JCO.2012.44.2137","article-title":"Follicular lymphoma cells induce changes in T-cell gene expression and function: Potential impact on survival and risk of transformation","volume":"31","author":"Kiaii","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1182\/blood-2006-04-018218","article-title":"High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma","volume":"108","author":"Carreras","year":"2006","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1200\/JCO.2008.18.0513","article-title":"High numbers of tumor-infiltrating programmed cell death 1-positive regulatory lymphocytes are associated with improved overall survival in follicular lymphoma","volume":"27","author":"Carreras","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1126\/science.3874430","article-title":"Involvement of the bcl-2 gene in human follicular lymphoma","volume":"228","author":"Tsujimoto","year":"1985","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/(SICI)1098-2264(200001)27:1<85::AID-GCC11>3.0.CO;2-9","article-title":"Interphase FISH detection of BCL2 rearrangement in follicular lymphoma using breakpoint-flanking probes","volume":"27","author":"Vaandrager","year":"2000","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1200\/JCO.2013.52.8190","article-title":"t(14;18) translocation: A predictive blood biomarker for follicular lymphoma","volume":"32","author":"Roulland","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1182\/blood.V85.9.2528.bloodjournal8592528","article-title":"Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals","volume":"85","author":"Limpens","year":"1995","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/sj.leu.2404035","article-title":"Long-term clonal persistence and evolution of t(14;18)-bearing B cells in healthy individuals","volume":"20","author":"Roulland","year":"2006","journal-title":"Leukemia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1080\/15592294.2017.1282587","article-title":"Follicular lymphoma, a B cell malignancy addicted to epigenetic mutations","volume":"12","author":"Korfi","year":"2017","journal-title":"Epigenetics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1182\/blood-2012-09-457283","article-title":"Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma","volume":"121","author":"Green","year":"2013","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/ng.2856","article-title":"Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma","volume":"46","author":"Okosun","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/S1470-2045(15)00169-2","article-title":"Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: A retrospective analysis of a prospective clinical trial and validation in a population-based registry","volume":"16","author":"Pastore","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nature10351","article-title":"Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma","volume":"476","author":"Morin","year":"2011","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/nm.3943","article-title":"The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development","volume":"21","author":"Boss","year":"2015","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1158\/2159-8290.CD-16-1417","article-title":"The CREBBP acetyltransferase is a haploinsufficient tumor suppressor in B-cell lymphoma","volume":"7","author":"Zhang","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1038\/nm.3940","article-title":"Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis","volume":"21","author":"Zhang","year":"2015","journal-title":"Nat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nature09730","article-title":"Inactivating mutations of acetyltransferase genes in B-cell lymphoma","volume":"471","author":"Pasqualucci","year":"2011","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1038\/ncb3597","article-title":"Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors","volume":"19","author":"Horton","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"E1116","DOI":"10.1073\/pnas.1501199112","article-title":"Mutations in early follicular lymphoma progenitors are associated with suppressed antigen presentation","volume":"112","author":"Green","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1182\/blood-2018-08-862292","article-title":"Single-cell RNA-Seq of follicular lymphoma reveals malignant B-cell types and coexpression of T-cell immune checkpoints","volume":"133","author":"Andor","year":"2019","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1158\/2159-8290.CD-16-0975","article-title":"CREBBP Inactivation Promotes the Development of HDAC3-Dependent Lymphomas","volume":"7","author":"Jiang","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1158\/2159-8290.CD-19-0116","article-title":"Selective Inhibition of HDAC3 Targets Synthetic Vulnerabilities and Activates Immune Surveillance in Lymphoma","volume":"10","author":"Mondello","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1007\/s13238-020-00694-x","article-title":"HDAC inhibitors overcome immunotherapy resistance in B-cell lymphoma","volume":"11","author":"Wang","year":"2020","journal-title":"Protein Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1200\/JCO.2010.32.1398","article-title":"Phase II study of vorinostat for treatment of relapsed or refractory indolent non-hodgkin\u2019s lymphoma and mantle cell lymphoma","volume":"29","author":"Kirschbaum","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1111\/bjh.12819","article-title":"A multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma","volume":"165","author":"Ogura","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1158\/1078-0432.CCR-15-0624","article-title":"A phase I\/II multicenter, open-label study of the oral histone deacetylase inhibitor abexinostat in relapsed\/refractory lymphoma","volume":"22","author":"Evens","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6558","DOI":"10.18632\/oncotarget.2289","article-title":"HDAC inhibitors and immunotherapy; A double edged sword?","volume":"5","author":"Kroesen","year":"2014","journal-title":"Oncotarget"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Morschhauser, F., Tilly, H., Chaidos, A., McKay, P., Phillips, T., Assouline, S., Batlevi, C.L., Campbell, P., Ribrag, V., and Damaj, G.L. (2020). Tazemetostat for patients with relapsed or refractory follicular lymphoma: An open-label, single-arm, multicentre, phase 2 trial. Lancet Oncol.","DOI":"10.1016\/S1470-2045(20)30441-1"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4740","DOI":"10.1200\/JCO.2010.29.2813","article-title":"Temsirolimus has activity in non-mantle cell non-Hodgkin\u2019s lymphoma subtypes: The University of Chicago phase II consortium","volume":"28","author":"Smith","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e398","DOI":"10.1097\/HS9.0000000000000398","article-title":"Final Results of a Phase I\/II Trial of the Combination Bendamustine and Rituximab With Temsirolimus (BeRT) in Relapsed Mantle Cell Lymphoma and Follicular Lymphoma","volume":"4","author":"Hess","year":"2020","journal-title":"HemaSphere"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3465","DOI":"10.1002\/cncr.29502","article-title":"A phase 2 study of weekly temsirolimus and bortezomib for relapsed or refractory B-cell non-Hodgkin lymphoma: A Wisconsin Oncology Network study","volume":"121","author":"Fenske","year":"2015","journal-title":"Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1182\/blood-2016-12-757740","article-title":"Idelalisib is effective in patients with high-risk follicular lymphoma and early relapse after initial chemoimmunotherapy","volume":"129","author":"Gopal","year":"2017","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4217","DOI":"10.1182\/bloodadvances.2020001584","article-title":"PI3Kd inhibition reshapes follicular lymphoma-immune microenvironment cross talk and unleashes the activity of venetoclax","volume":"4","author":"Serrat","year":"2020","journal-title":"Blood Adv."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1093\/annonc\/mdx289","article-title":"Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma","volume":"28","author":"Dreyling","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1200\/JCO.18.00915","article-title":"DYNAMO: A Phase II study of duvelisib (IPI-145) in patients with refractory indolent non-hodgkin lymphoma","volume":"37","author":"Flinn","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1182\/blood-2017-09-804641","article-title":"Single-agent ibrutinib in relapsed or refractory follicular lymphoma: A phase 2 consortium trial","volume":"131","author":"Bartlett","year":"2018","journal-title":"Blood"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/bjh.16424","article-title":"The combination of ibrutinib and rituximab demonstrates activity in first-line follicular lymphoma","volume":"189","author":"Fowler","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1182\/blood-2009-08-236471","article-title":"Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia","volume":"115","author":"Friedberg","year":"2010","journal-title":"Blood"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"E90","DOI":"10.1002\/ajh.25387","article-title":"Efficacy and safety of the dual SYK\/JAK inhibitor cerdulatinib in patients with relapsed or refractory B-cell malignancies: Results of a phase I study","volume":"94","author":"Hamlin","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.cell.2016.08.032","article-title":"Loss of the HVEM Tumor Suppressor in Lymphoma and Restoration by Modified CAR-T Cells","volume":"167","author":"Boice","year":"2016","journal-title":"Cell"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Armand, P., Janssens, A.M., Gritti, G., Radford, J., Timmerman, J.M., Pinto, A., Mercadal Vilchez, S., Johnson, P.W.M., Cunningham, D., and Leonard, J.P. (2020). Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed\/refractory follicular lymphoma. Blood.","DOI":"10.1182\/blood.2019004753"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S1470-2045(13)70551-5","article-title":"Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: A single group, open-label, phase 2 trial","volume":"15","author":"Westin","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1002\/ajh.25757","article-title":"Urelumab alone or in combination with rituximab in patients with relapsed or refractory B-cell lymphoma","volume":"95","author":"Timmerman","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Chen, Y.P., Kim, H.J., Wu, H., Price-Troska, T., Villasboas, J.C., Jalali, S., Feldman, A.L., Novak, A.J., Yang, Z.Z., and Ansell, S.M. (2019). SIRP\u03b1 expression delineates subsets of intratumoral monocyte\/macrophages with different functional and prognostic impact in follicular lymphoma. Blood Cancer J., 9.","DOI":"10.1038\/s41408-019-0246-0"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1056\/NEJMoa1807315","article-title":"CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin\u2019s Lymphoma","volume":"379","author":"Advani","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1182\/blood-2013-04-496893","article-title":"EZH2 mutations are frequent and represent an early event in follicular lymphoma","volume":"122","author":"Grossmann","year":"2013","journal-title":"Blood"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"20980","DOI":"10.1073\/pnas.1012525107","article-title":"Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas","volume":"107","author":"Sneeringer","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.ccr.2013.04.011","article-title":"EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation","volume":"23","author":"Popovic","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.ccell.2016.07.006","article-title":"EZH2 and BCL6 Cooperate to Assemble CBX8-BCOR Complex to Repress Bivalent Promoters, Mediate Germinal Center Formation and Lymphomagenesis","volume":"30","author":"Teater","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.ccell.2020.04.004","article-title":"Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response","volume":"37","author":"Teater","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/nchembio.1084","article-title":"A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells","volume":"8","author":"Knutson","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature11606","article-title":"EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations","volume":"492","author":"McCabe","year":"2012","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S1470-2045(18)30145-1","article-title":"Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: A first-in-human, open-label, phase 1 study","volume":"19","author":"Italiano","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.ccr.2011.11.006","article-title":"Combined Genetic Inactivation of \u03b22-Microglobulin and CD58 Reveals Frequent Escape from Immune Recognition in Diffuse Large B Cell Lymphoma","volume":"20","author":"Lieu","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.celrep.2013.12.027","article-title":"Genetics of Follicular Lymphoma Transformation","volume":"6","author":"Pasqualucci","year":"2014","journal-title":"Cell Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pmed.1002197","article-title":"Histological Transformation and Progression in Follicular Lymphoma: A Clonal Evolution Study","volume":"13","author":"Kridel","year":"2016","journal-title":"PLoS Med."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Bararia, D., Hildebrand, J.A., Stolz, S., Haebe, S., Alig, S., Trevisani, C.P., Osorio-Barrios, F., Bartoschek, M.D., Mentz, M., and Pastore, A. (2020). Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma. Cell Rep., 31.","DOI":"10.1016\/j.celrep.2020.107522"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S1074-7613(00)80249-6","article-title":"Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading","volume":"4","author":"Riese","year":"1996","journal-title":"Immunity"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.ccell.2020.03.016","article-title":"Cathepsin S Regulates Antigen Processing and T Cell Activity in Non-Hodgkin Lymphoma","volume":"37","author":"Dheilly","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"9166","DOI":"10.1158\/0008-5472.CAN-10-2460","article-title":"Acquired TNFRSF14 mutations in follicular lymphoma are associated with worse prognosis","volume":"70","author":"Cheung","year":"2010","journal-title":"Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/leu.2011.266","article-title":"High rate of TNFRSF14 gene alterations related to 1p36 region in de novo follicular lymphoma and impact on prognosis","volume":"26","author":"Launay","year":"2012","journal-title":"Leukemia"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/ng.3473","article-title":"Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma","volume":"48","author":"Okosun","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5383","DOI":"10.1158\/1078-0432.CCR-16-0609","article-title":"Recurrent mutations in the MTOR regulator RRAGC in follicular lymphoma","volume":"22","author":"Ying","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/s42255-019-0098-8","article-title":"Oncogenic Rag GTPase signalling enhances B cell activation and drives follicular lymphoma sensitive to pharmacological inhibition of mTOR","volume":"1","author":"Carreras","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.4049\/jimmunol.144.7.2550","article-title":"Induction of proliferation of human follicular (b type) lymphoma cells by cognate interaction with cd4+ t cell clones","volume":"144","author":"Umetsu","year":"1990","journal-title":"J. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/joim.12600","article-title":"Targeting of B-cell receptor signalling in B-cell malignancies","volume":"282","author":"Jerkeman","year":"2017","journal-title":"J. Int. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"6681","DOI":"10.4049\/jimmunol.1201363","article-title":"Cross Talk between Follicular Th Cells and Tumor Cells in Human Follicular Lymphoma Promotes Immune Evasion in the Tumor Microenvironment","volume":"190","author":"Rawal","year":"2013","journal-title":"J. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1182\/blood-2009-07-235598","article-title":"The architectural pattern of FOXP3-positive T cells in follicular lymphoma is an independent predictor of survival and histologic transformation","volume":"115","author":"Farinha","year":"2010","journal-title":"Blood"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"E6400","DOI":"10.1073\/pnas.1705551114","article-title":"A distinct subpopulation of CD25 \u2212 T-follicular regulatory cells localizes in the germinal centers","volume":"114","author":"Wing","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1182\/blood-2013-11-538546","article-title":"Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-d, as therapy for previously treated indolent non-Hodgkin lymphoma","volume":"123","author":"Flinn","year":"2014","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1056\/NEJMoa1314583","article-title":"PI3K\u03b4 inhibition by idelalisib in patients with relapsed indolent lymphoma","volume":"370","author":"Gopal","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Smolewski, P., and Rydygier, D. (2020). Efficacy and safety of idelalisib for the treatment of indolent B-cell malignancies. Expert Opin. Pharmacother., 1\u201312.","DOI":"10.1080\/14656566.2020.1791083"},{"key":"ref_100","first-page":"3079","article-title":"PI3K Orchestrates T Follicular Helper Cell Differentiation in a Context Dependent Manner: Implications for Autoimmunity","volume":"1","author":"Abboud","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.4049\/jimmunol.1701703","article-title":"The PI3K p110\u03b4 Isoform Inhibitor Idelalisib Preferentially Inhibits Human Regulatory T Cell Function","volume":"202","author":"Chellappa","year":"2019","journal-title":"J. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.2217\/fon-2018-0881","article-title":"Duvelisib: A new phosphoinositide-3-kinase inhibitor in chronic lymphocytic leukemia","volume":"15","author":"Frustaci","year":"2019","journal-title":"Futur. Oncol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Mhibik, M., Wiestner, A., and Sun, C. (2020). Harnessing the Effects of BTKi on T Cells for Effective Immunotherapy against CLL. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010068"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1172\/JCI89756","article-title":"Ibrutinib treatment improves T cell number and function in CLL patients","volume":"127","author":"Long","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1158\/1078-0432.CCR-18-1047","article-title":"Cerdulatinib Pharmacodynamics and Relationships to Tumor Response Following Oral Dosing in Patients with Relapsed\/Refractory B-cell Malignancies","volume":"15","author":"Coffey","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1182\/blood-2012-04-421826","article-title":"High PD-1 expression and suppressed cytokine signaling distinguish T cells infiltrating follicular lymphoma tumors from peripheral T cells","volume":"121","author":"Myklebust","year":"2013","journal-title":"Blood"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nrclinonc.2015.187","article-title":"Novel immunotherapies in lymphoid malignancies","volume":"13","author":"Batlevi","year":"2016","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.immuni.2016.05.001","article-title":"Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation","volume":"44","author":"Anderson","year":"2016","journal-title":"Immunity"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e000911","DOI":"10.1136\/jitc-2020-000911","article-title":"Tim-3 finds its place in the cancer immunotherapy landscape","volume":"8","author":"Acharya","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e281-10","DOI":"10.1038\/bcj.2015.1","article-title":"PD-1 expression defines two distinct T-cell sub-populations in follicular lymphoma that differentially impact patient survival","volume":"5","author":"Yang","year":"2015","journal-title":"Blood Cancer J."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e1224044","DOI":"10.1080\/2162402X.2016.1224044","article-title":"Impaired functional responses in follicular lymphoma CD8+TIM-3+ T lymphocytes following TCR engagement","volume":"5","author":"Gravelle","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e1026530","DOI":"10.1080\/2162402X.2015.1026530","article-title":"Several immune escape patterns in non-Hodgkin\u2019s lymphomas","volume":"4","author":"Laurent","year":"2015","journal-title":"Oncoimmunology"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/hon.2438_128","article-title":"Expression of Lag-3 Defines Exhaustion of Intratumoral Pd-1 + T Cells and Correlates With Poor Outcome in Follicular Lymphoma","volume":"35","author":"Yang","year":"2017","journal-title":"Hematol. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5371","DOI":"10.1182\/blood-2011-04-345777","article-title":"Distribution, function, and prognostic value of cytotoxic T lymphocytes in follicular lymphoma: A 3-D tissue-imaging study","volume":"118","author":"Laurent","year":"2011","journal-title":"Blood"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1158\/2326-6066.CIR-18-0351","article-title":"TIGIT and PD-1 Mark Intratumoral T Cells with Reduced Effector Function in B-cell Non-Hodgkin Lymphoma","volume":"7","author":"Josefsson","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1158\/1078-0432.CCR-17-2337","article-title":"T Cells Expressing Checkpoint Receptor TIGIT Are Enriched in Follicular Lymphoma Tumors and Characterized by Reversible Suppression of T-cell Receptor Signaling","volume":"24","author":"Josefsson","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2698","DOI":"10.1200\/JCO.2015.65.9789","article-title":"Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study","volume":"34","author":"Lesokhin","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Armand, P., Lesokhin, A., Borrello, I., Timmerman, J., Gutierrez, M., Zhu, L., Popa McKiver, M., and Ansell, S.M. (2020). A phase 1b study of dual PD-1 and CTLA-4 or KIR blockade in patients with relapsed\/refractory lymphoid malignancies. Leukemia.","DOI":"10.1038\/s41375-020-0939-1"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"5217","DOI":"10.1158\/1078-0432.CCR-20-0558","article-title":"TIGIT Expression Is Associated with T-cell Suppression and Exhaustion and Predicts Clinical Outcome and Anti-PD-1 Response in Follicular Lymphoma","volume":"26","author":"Yang","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/bjh.12630","article-title":"Phase IA\/II, multicentre, open-label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non-Hodgkin or Hodgkin lymphoma","volume":"164","author":"Fanale","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.4161\/onci.22196","article-title":"Myeloid cells prime drivers of tumor progression","volume":"1","author":"Toh","year":"2012","journal-title":"Oncoimmunology"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1182\/bloodadvances.2016000786","article-title":"Mutation load and an effector T-cell gene signature may distinguish immunologically distinct and clinically relevant lymphoma subsets","volume":"1","author":"Bolen","year":"2017","journal-title":"Blood Adv."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"575","DOI":"10.3109\/10428194.2011.637211","article-title":"The absolute monocyte count is associated with overall survival in patients newly diagnosed with follicular lymphoma","volume":"53","author":"Wilcox","year":"2012","journal-title":"Leuk. Lymphoma"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/j.leukres.2013.07.015","article-title":"Absolute monocyte count in follicular lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone","volume":"37","author":"Watanabe","year":"2013","journal-title":"Leuk. Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/bmjopen-2017-017904","article-title":"Prognostic value of lymphocyte-To-monocyte ratio and neutrophil-To-lymphocyte ratio in follicular lymphoma: A retrospective cohort study","volume":"7","author":"Lee","year":"2017","journal-title":"BMJ Open"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1080\/10428194.2020.1821010","article-title":"A low lymphocyte-to-monocyte ratio is an independent predictor of poorer survival and higher risk of histological transformation in follicular lymphoma","volume":"62","author":"Mozas","year":"2021","journal-title":"Leuk. Lymphoma"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.coi.2010.01.009","article-title":"Macrophages, innate immunity and cancer: Balance, tolerance, and diversity","volume":"22","author":"Mantovani","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fonc.2019.01512","article-title":"Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice","volume":"9","author":"Jayasingam","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1182\/blood-2005-04-1565","article-title":"Analysis of multiple biomarkers shows that lymphoma-associated macrophage (LAM) content is an independent predictor of survival in follicular lymphoma (FL)","volume":"106","author":"Farinha","year":"2005","journal-title":"Blood"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"5784","DOI":"10.1158\/1078-0432.CCR-07-0778","article-title":"A high tumor-associated macrophage content predicts favorable outcome in follicular lymphoma patients treated with rituximab and cyclophosphamide- doxorubicin-vincristine-prednisone","volume":"13","author":"Taskinen","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1200\/JCO.2007.12.8298","article-title":"High numbers of tumor-associated macrophages have an adverse prognostic value that can be circumvented by rituximab in patients with follicular lymphoma enrolled onto the GELA-GOELAMS FL-2000 trial","volume":"26","author":"Canioni","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"5053","DOI":"10.1182\/blood-2009-11-253260","article-title":"Increased angiogenic sprouting in poor prognosis FL is associated with elevated numbers of CD163+ macrophages within the immediate sprouting microenvironment","volume":"115","author":"Clear","year":"2010","journal-title":"Blood"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3428","DOI":"10.1158\/1078-0432.CCR-14-3253","article-title":"The Prognostic Impact of CD163-Positive Macrophages in Follicular Lymphoma: A Study from the BC Cancer Agency and the Lymphoma Study Association","volume":"21","author":"Kridel","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.3324\/haematol.2017.165415","article-title":"Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome 18 in follicular lymphoma: A study by the Lunenburg Lymphoma Biomarker Consortium","volume":"102","author":"Stevens","year":"2017","journal-title":"Haematologica"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1182\/blood-2011-09-379214","article-title":"Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling","volume":"119","author":"Hume","year":"2012","journal-title":"Blood"},{"key":"ref_136","first-page":"1","article-title":"CSF1R protein expression in reactive lymphoid tissues and lymphoma: Its relevance in classical Hodgkin lymphoma","volume":"10","author":"Roncador","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fimmu.2020.00018","article-title":"Advances in Anti-Tumor Treatments Targeting the CD47\/SIRP\u03b1 Axis","volume":"11","author":"Zhang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1038\/s41375-019-0463-3","article-title":"CSF1R and BTK inhibitions as novel strategies to disrupt the dialog between mantle cell lymphoma and macrophages","volume":"33","author":"Papin","year":"2019","journal-title":"Leukemia"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1182\/blood-2018-03-838946","article-title":"CSF1R inhibitors exhibit antitumor activity in acute myeloid leukemia by blocking paracrine signals from support cells","volume":"133","author":"Edwards","year":"2019","journal-title":"Blood"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nature19834","article-title":"PI3K\u03b3 is a molecular switch that controls immune suppression HHS Public Access","volume":"539","author":"Kaneda","year":"2016","journal-title":"Nature"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1182\/blood-2017-08-802470","article-title":"Activity of the PI3K-d,g inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma","volume":"131","author":"Horwitz","year":"2018","journal-title":"Blood"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1158\/1078-0432.CCR-18-1133","article-title":"Targeting cancer cells and tumor microenvironment in preclinical and clinical models of Hodgkin lymphoma using the dual PI3Kd\/G inhibitor RP6530","volume":"25","author":"Locatelli","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1182\/blood-2017-05-786566","article-title":"Duvelisib, a novel oral dual inhibitor of PI3K-d,g, is clinically active in advanced hematologic malignancies","volume":"131","author":"Flinn","year":"2018","journal-title":"Blood"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1093\/annonc\/mdn163","article-title":"Neutrophil role in in vivo anti-lymphoma activity of rituximab: FCGR3B-NA1\/NA2 polymorphism does not influence response and survival after rituximab treatment","volume":"19","author":"Cartron","year":"2008","journal-title":"Ann. Oncol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"16471","DOI":"10.18632\/oncotarget.4106","article-title":"Neutrophils trigger a NF-\u039aB dependent polarization of tumorsupportive stromal cells in germinal center B-cell lymphomas","volume":"6","author":"Guilloton","year":"2015","journal-title":"Oncotarget"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"72818","DOI":"10.18632\/oncotarget.20350","article-title":"Neutrophils protect lymphoma cells against cytotoxic and targeted therapies through CD11b\/ICAM-1 binding","volume":"8","author":"Hirz","year":"2017","journal-title":"Oncotarget"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/4\/641\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:20:04Z","timestamp":1760160004000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/4\/641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,5]]},"references-count":146,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["cancers13040641"],"URL":"https:\/\/doi.org\/10.3390\/cancers13040641","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,5]]}}}