{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T16:26:44Z","timestamp":1790526404943,"version":"4.1.0"},"reference-count":112,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"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>Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) characterized by the translocation t(11;14) (q13;q32) and a poor response to rituximab\u2013anthracycline-based chemotherapy. High-dose cytarabine-based regimens offer a durable response, but an important number of MCL patients are not eligible for intensive treatment and are ideal candidates for novel targeted therapies (such as BTK, proteasome or BCL2 inhibitors, Immunomodulatory Drugs (IMiDs), bispecific antibodies, or CAR-T cell therapy). On the bench side, several studies aiming to integrate the tumor within its ecosystem highlighted a critical role of the tumor microenvironment (TME) in the expansion and resistance of MCL. This led to important insights into the role of the TME in the management of MCL, including potential targets and biomarkers. Indeed, targeted agents often have a combined mechanism of action on the tumor B cell but also on the tumor microenvironment. The aim of this review is to briefly describe the current knowledge on the biology of the TME in MCL and expose the results of the different therapeutic strategies integrating the TME in this disease.<\/jats:p>","DOI":"10.3390\/cancers14133229","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T20:53:02Z","timestamp":1656622382000},"page":"3229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Tumor Microenvironment and Immunotherapy-Based Approaches in Mantle Cell Lymphoma"],"prefix":"10.3390","volume":"14","author":[{"given":"Khalil","family":"Saleh","sequence":"first","affiliation":[{"name":"Department of Hematology, Gustave Roussy Cancer Campus, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Cheminant","sequence":"additional","affiliation":[{"name":"Department of Hematology, Necker Hospital, Assistance Publique des Hopitaux de Paris (APHP), 75004 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2199-752X","authenticated-orcid":false,"given":"David","family":"Chiron","sequence":"additional","affiliation":[{"name":"Nantes Universite, Inserm, CNRS, Universite d\u2019Angers, CRCI2NA, 44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Burroni","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cochin Hospital, Assistance Publique des Hopitaux de Paris (APHP), 75004 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Ribrag","sequence":"additional","affiliation":[{"name":"Department of Hematology, Gustave Roussy Cancer Campus, 94805 Villejuif, France"},{"name":"Departement d\u2019Innovation Therapeutique et d\u2019Essais Precoces (DITEP), Gustave Roussy Cancer Campus, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mentine","family":"Sarkozy","sequence":"additional","affiliation":[{"name":"Departement d\u2019Innovation Therapeutique et d\u2019Essais Precoces (DITEP), Gustave Roussy Cancer Campus, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"iv62","DOI":"10.1093\/annonc\/mdx223","article-title":"Newly Diagnosed and Relapsed Mantle Cell Lymphoma: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up","volume":"28","author":"Dreyling","year":"2017","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1002\/cncr.23608","article-title":"Incidence Trends of Mantle Cell Lymphoma in the United States between 1992 and 2004","volume":"113","author":"Zhou","year":"2008","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1038\/bjc.2011.450","article-title":"Incidence of Haematological Malignancy by Sub-Type: A Report from the Haematological Malignancy Research Network","volume":"105","author":"Smith","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1200\/JCO.2008.16.8435","article-title":"Improvement of Overall Survival in Advanced Stage Mantle Cell Lymphoma","volume":"27","author":"Herrmann","year":"2009","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1182\/blood-2016-01-643569","article-title":"The 2016 Revision of the World Health Organization Classification of Lymphoid Neoplasms","volume":"127","author":"Swerdlow","year":"2016","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e153283","DOI":"10.1172\/JCI153283","article-title":"Genomic and Transcriptomic Profiling Reveals Distinct Molecular Subsets Associated with Outcomes in Mantle Cell Lymphoma","volume":"132","author":"Yi","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/bjh.17419","article-title":"Mantle Cell Lymphoma\u2014Advances in Molecular Biology, Prognostication and Treatment Approaches","volume":"195","author":"Silkenstedt","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1056\/NEJMoa1306220","article-title":"Targeting BTK with Ibrutinib in Relapsed or Refractory Mantle-Cell Lymphoma","volume":"369","author":"Wang","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/S0140-6736(15)00667-4","article-title":"Ibrutinib versus Temsirolimus in Patients with Relapsed or Refractory Mantle-Cell Lymphoma: An International, Randomised, Open-Label, Phase 3 Study","volume":"387","author":"Dreyling","year":"2016","journal-title":"Lancet Lond. Engl."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0140-6736(17)33108-2","article-title":"Acalabrutinib in Relapsed or Refractory Mantle Cell Lymphoma (ACE-LY-004): A Single-Arm, Multicentre, Phase 2 Trial","volume":"391","author":"Wang","year":"2018","journal-title":"Lancet Lond. Engl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4216","DOI":"10.1158\/1078-0432.CCR-19-3703","article-title":"Treatment of Patients with Relapsed or Refractory Mantle-Cell Lymphoma with Zanubrutinib, a Selective Inhibitor of Bruton\u2019s Tyrosine Kinase","volume":"26","author":"Song","year":"2020","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4867","DOI":"10.1200\/JCO.2006.07.9665","article-title":"Multicenter Phase II Study of Bortezomib in Patients with Relapsed or Refractory Mantle Cell Lymphoma","volume":"24","author":"Fisher","year":"2006","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5347","DOI":"10.1200\/JCO.2005.13.466","article-title":"Phase II Trial of Single-Agent Temsirolimus (CCI-779) for Relapsed Mantle Cell Lymphoma","volume":"23","author":"Witzig","year":"2005","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3822","DOI":"10.1200\/JCO.2008.20.7977","article-title":"Phase III Study to Evaluate Temsirolimus Compared with Investigator\u2019s Choice Therapy for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma","volume":"27","author":"Hess","year":"2009","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S1470-2045(15)00559-8","article-title":"Lenalidomide versus Investigator\u2019s Choice in Relapsed or Refractory Mantle Cell Lymphoma (MCL-002; SPRINT): A Phase 2, Randomised, Multicentre Trial","volume":"17","author":"Lamy","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1182\/blood-2018-06-860593","article-title":"A Pilot Study of Lower Doses of Ibrutinib in Patients with Chronic Lymphocytic Leukemia","volume":"132","author":"Chen","year":"2018","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1182\/blood-2013-02-482125","article-title":"Egress of CD19(+)CD5(+) Cells into Peripheral Blood Following Treatment with the Bruton Tyrosine Kinase Inhibitor Ibrutinib in Mantle Cell Lymphoma Patients","volume":"122","author":"Chang","year":"2013","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"39218","DOI":"10.18632\/oncotarget.16836","article-title":"The Bruton\u2019s Tyrosine Kinase Inhibitor Ibrutinib Exerts Immunomodulatory Effects through Regulation of Tumor-Infiltrating Macrophages","volume":"8","author":"Ping","year":"2017","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1056\/NEJMoa1914347","article-title":"KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma","volume":"382","author":"Wang","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1182\/blood-2021-146845","article-title":"Glofitamab Monotherapy Provides Durable Responses after Fixed-Length Dosing in Relapsed\/Refractory (R\/R) Non-Hodgkin Lymphoma (NHL) Patients (Pts)","volume":"138","author":"Dickinson","year":"2021","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sadeghi, L., and Wright, A.P. (2021). Migration and Adhesion of B-Lymphocytes to Specific Microenvironments in Mantle Cell Lymphoma: Interplay between Signaling Pathways and the Epigenetic Landscape. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126247"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.1172\/JCI61272","article-title":"Molecular Pathogenesis of Mantle Cell Lymphoma","volume":"122","author":"Jares","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1182\/blood.2020005289","article-title":"Genomic and Epigenomic Insights into the Origin, Pathogenesis, and Clinical Behavior of Mantle Cell Lymphoma Subtypes","volume":"136","author":"Nadeu","year":"2020","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1073\/pnas.0510441103","article-title":"Mutation and Genomic Deletion Status of Ataxia Telangiectasia Mutated (ATM) and P53 Confer Specific Gene Expression Profiles in Mantle Cell Lymphoma","volume":"103","author":"Greiner","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1182\/blood-2011-11-391474","article-title":"Whole Transcriptome Sequencing Reveals Recurrent NOTCH1 Mutations in Mantle Cell Lymphoma","volume":"119","author":"Kridel","year":"2012","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"18250","DOI":"10.1073\/pnas.1314608110","article-title":"Landscape of Somatic Mutations and Clonal Evolution in Mantle Cell Lymphoma","volume":"110","author":"Navarro","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.ccell.2016.09.014","article-title":"Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage","volume":"30","author":"Beekman","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2808","DOI":"10.1182\/blood-2016-06-720490","article-title":"Rational Targeted Therapies to Overcome Microenvironment-Dependent Expansion of Mantle Cell Lymphoma","volume":"128","author":"Chiron","year":"2016","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1182\/blood-2015-11-681460","article-title":"Pathogenic Role of B-Cell Receptor Signaling and Canonical NF-\u039aB Activation in Mantle Cell Lymphoma","volume":"128","author":"Saba","year":"2016","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"645","DOI":"10.3389\/fonc.2018.00645","article-title":"BCL2-Family Dysregulation in B-Cell Malignancies: From Gene Expression Regulation to a Targeted Therapy Biomarker","volume":"8","author":"Tessoulin","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1002\/ijc.29326","article-title":"Inhibitors of BCR Signalling Interrupt the Survival Signal Mediated by the Micro-Environment in Mantle Cell Lymphoma","volume":"136","author":"Bernard","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3324\/haematol.2017.177162","article-title":"Inhibition of Focal Adhesion Kinase Overcomes Resistance of Mantle Cell Lymphoma to Ibrutinib in the Bone Marrow Microenvironment","volume":"103","author":"Rudelius","year":"2018","journal-title":"Haematologica"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8750","DOI":"10.18632\/oncotarget.3275","article-title":"Biological Rational for Sequential Targeting of Bruton Tyrosine Kinase and Bcl-2 to Overcome CD40-Induced ABT-199 Resistance in Mantle Cell Lymphoma","volume":"6","author":"Chiron","year":"2015","journal-title":"Oncotarget"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/bjh.13275","article-title":"Ibrutinib-Associated Lymphocytosis Corresponds to Bone Marrow Involvement in Mantle Cell Lymphoma","volume":"170","author":"Furtado","year":"2015","journal-title":"Br. J. Haematol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/sj.leu.2401664","article-title":"Proliferative Response of Mantle Cell Lymphoma Cells Stimulated by CD40 Ligation and IL-4","volume":"14","author":"Castillo","year":"2000","journal-title":"Leukemia"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Decombis, S., Papin, A., Bellanger, C., Sortais, C., Dousset, C., Le Bris, Y., Riveron, T., Blandin, S., Hulin, P., and Tessoulin, B. (2022). The IL32\/BAFF Axis Supports Prosurvival Dialogs in the Lymphoma Ecosystem and Is Disrupted by NIK Inhibition. Haematologica, Online ahead of print.","DOI":"10.3324\/haematol.2021.279800"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41591-018-0243-z","article-title":"Dynamic Molecular Monitoring Reveals That SWI-SNF Mutations Mediate Resistance to Ibrutinib plus Venetoclax in Mantle Cell Lymphoma","volume":"25","author":"Agarwal","year":"2019","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nm.3435","article-title":"Pharmacological and Genomic Profiling Identifies NF-\u039aB-Targeted Treatment Strategies for Mantle Cell Lymphoma","volume":"20","author":"Rahal","year":"2014","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1182\/blood.2020008727","article-title":"Ibrutinib, Obinutuzumab, and Venetoclax in Relapsed and Untreated Patients with Mantle Cell Lymphoma: A Phase 1\/2 Trial","volume":"137","author":"Morschhauser","year":"2021","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/bjh.17366","article-title":"Infiltration of CD163-, PD-L1- and FoxP3-Positive Cells Adversely Affects Outcome in Patients with Mantle Cell Lymphoma Independent of Established Risk Factors","volume":"193","author":"Rodrigues","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_41","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_42","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1084\/jem.189.11.1747","article-title":"BAFF, a Novel Ligand of the Tumor Necrosis Factor Family, Stimulates B Cell Growth","volume":"189","author":"Schneider","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.humpath.2005.08.005","article-title":"BAFF-R, the Major B Cell-Activating Factor Receptor, Is Expressed on Most Mature B Cells and B-Cell Lymphoproliferative Disorders","volume":"36","author":"Rodig","year":"2005","journal-title":"Hum. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/eji.200636623","article-title":"TACI Attenuates Antibody Production Costimulated by BAFF-R and CD40","volume":"37","author":"Sakurai","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/j.1600-065X.2011.01067.x","article-title":"Signaling by the Tumor Necrosis Factor Receptor Superfamily in B-Cell Biology and Disease","volume":"244","author":"Rickert","year":"2011","journal-title":"Immunol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.semcancer.2011.09.006","article-title":"The Microenvironment in Mantle Cell Lymphoma: Cellular and Molecular Pathways and Emerging Targeted Therapies","volume":"21","author":"Burger","year":"2011","journal-title":"Semin. Cancer Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1182\/blood-2008-10-185827","article-title":"Mantle Cell Lymphoma Cells Express High Levels of CXCR4, CXCR5, and VLA-4 (CD49d): Importance for Interactions with the Stromal Microenvironment and Specific Targeting","volume":"113","author":"Kurtova","year":"2009","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1182\/blood-2006-11-060350","article-title":"Cell Adhesion Induces P27Kip1-Associated Cell-Cycle Arrest through down-Regulation of the SCFSkp2 Ubiquitin Ligase Pathway in Mantle-Cell and Other Non-Hodgkin B-Cell Lymphomas","volume":"110","author":"Lwin","year":"2007","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/leu.2008.266","article-title":"Lymphoma Cell Adhesion-Induced Expression of B Cell-Activating Factor of the TNF Family in Bone Marrow Stromal Cells Protects Non-Hodgkin\u2019s B Lymphoma Cells from Apoptosis","volume":"23","author":"Lwin","year":"2009","journal-title":"Leukemia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1158\/1078-0432.CCR-15-0987","article-title":"ROS-Induced CXCR4 Signaling Regulates Mantle Cell Lymphoma (MCL) Cell Survival and Drug Resistance in the Bone Marrow Microenvironment via Autophagy","volume":"22","author":"Chen","year":"2016","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.3324\/haematol.2011.040659","article-title":"Mesenchymal Stromal Cells Protect Mantle Cell Lymphoma Cells from Spontaneous and Drug-Induced Apoptosis through Secretion of B-Cell Activating Factor and Activation of the Canonical and Non-Canonical Nuclear Factor \u039aB Pathways","volume":"97","author":"Medina","year":"2012","journal-title":"Haematologica"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1893501","DOI":"10.1080\/2162402X.2021.1893501","article-title":"BAFF Receptor Antibody for Mantle Cell Lymphoma Therapy","volume":"10","author":"Zhang","year":"2021","journal-title":"Oncoimmunology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.3324\/haematol.2009.010264","article-title":"SOX11 Expression Is Highly Specific for Mantle Cell Lymphoma and Identifies the Cyclin D1-Negative Subtype","volume":"94","author":"Mozos","year":"2009","journal-title":"Haematologica"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5307","DOI":"10.1158\/0008-5472.CAN-12-1615","article-title":"Molecular Subsets of Mantle Cell Lymphoma Defined by the IGHV Mutational Status and SOX11 Expression Have Distinct Biologic and Clinical Features","volume":"72","author":"Navarro","year":"2012","journal-title":"Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1182\/blood-2012-06-438937","article-title":"SOX11 Regulates PAX5 Expression and Blocks Terminal B-Cell Differentiation in Aggressive Mantle Cell Lymphoma","volume":"121","author":"Vegliante","year":"2013","journal-title":"Blood"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1182\/blood-2014-04-569566","article-title":"SOX11 Promotes Tumor Angiogenesis through Transcriptional Regulation of PDGFA in Mantle Cell Lymphoma","volume":"124","author":"Palomero","year":"2014","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"100744","DOI":"10.1016\/j.tranon.2020.100744","article-title":"Inflammatory Infiltrate and Angiogenesis in Mantle Cell Lymphoma","volume":"13","author":"Annese","year":"2020","journal-title":"Transl. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1182\/blood-2017-04-776740","article-title":"SOX11 Promotes Tumor Protective Microenvironment Interactions through CXCR4 and FAK Regulation in Mantle Cell Lymphoma","volume":"130","author":"Balsas","year":"2017","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1182\/blood.2020010527","article-title":"SOX11, CD70, and Treg Cells Configure the Tumor-Immune Microenvironment of Aggressive Mantle Cell Lymphoma","volume":"138","author":"Balsas","year":"2021","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.3324\/haematol.2012.071340","article-title":"Immune Evasion of Mantle Cell Lymphoma: Expression of B7-H1 Leads to Inhibited T-Cell Response to and Killing of Tumor Cells","volume":"98","author":"Wang","year":"2013","journal-title":"Haematologica"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1080\/10428194.2019.1569231","article-title":"Modulation of Immune Checkpoint Molecule Expression in Mantle Cell Lymphoma","volume":"60","author":"Harrington","year":"2019","journal-title":"Leuk. Lymphoma"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1182\/blood-2017-07-740993","article-title":"PD-1 Expression and Clinical PD-1 Blockade in B-Cell Lymphomas","volume":"131","author":"Zhou","year":"2018","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1200\/JCO.2016.70.4320","article-title":"Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma","volume":"35","author":"Davids","year":"2017","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1056\/NEJMoa1715519","article-title":"Ibrutinib plus Venetoclax for the Treatment of Mantle-Cell Lymphoma","volume":"378","author":"Tam","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1056\/NEJMoa1805104","article-title":"Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma","volume":"379","author":"Morschhauser","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1158\/2643-3230.BCD-20-0105","article-title":"Avadomide Induces Degradation of ZMYM2 Fusion Oncoproteins in Hematologic Malignancies","volume":"2","author":"Renneville","year":"2021","journal-title":"Blood Cancer Discov."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.ccr.2012.05.024","article-title":"Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma","volume":"21","author":"Yang","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/bjh.12172","article-title":"Lenalidomide Efficacy in Activated B-Cell-like Subtype Diffuse Large B-Cell Lymphoma Is Dependent upon IRF4 and Cereblon Expression","volume":"160","author":"Zhang","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1111\/bjh.12708","article-title":"Immunomodulatory Agents Lenalidomide and Pomalidomide Co-Stimulate T Cells by Inducing Degradation of T Cell Repressors Ikaros and Aiolos via Modulation of the E3 Ubiquitin Ligase Complex CRL4(CRBN.)","volume":"164","author":"Gandhi","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ioannou, N., Jain, K., and Ramsay, A.G. (2021). Immunomodulatory Drugs for the Treatment of B Cell Malignancies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168572"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1182\/blood.2020006073","article-title":"Triggering Interferon Signaling in T Cells with Avadomide Sensitizes CLL to Anti-PD-L1\/PD-1 Immunotherapy","volume":"137","author":"Ioannou","year":"2021","journal-title":"Blood"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1182\/blood-2014-03-559591","article-title":"Lenalidomide Inhibits the Proliferation of CLL Cells via a Cereblon\/P21(WAF1\/Cip1)-Dependent Mechanism Independent of Functional P53","volume":"124","author":"Fecteau","year":"2014","journal-title":"Blood"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1182\/bloodadvances.2020003774","article-title":"Lenalidomide Triggers T-Cell Effector Functions in Vivo in Patients with Follicular Lymphoma","volume":"5","author":"Rossille","year":"2021","journal-title":"Blood Adv."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4650","DOI":"10.1158\/1078-0432.CCR-07-4405","article-title":"Lenalidomide Enhances Natural Killer Cell and Monocyte-Mediated Antibody-Dependent Cellular Cytotoxicity of Rituximab-Treated CD20+ Tumor Cells","volume":"14","author":"Wu","year":"2008","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.1200\/JCO.2013.49.2835","article-title":"Single-Agent Lenalidomide in Patients with Mantle-Cell Lymphoma Who Relapsed or Progressed after or Were Refractory to Bortezomib: Phase II MCL-001 (EMERGE) Study","volume":"31","author":"Goy","year":"2013","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e109","DOI":"10.1016\/S2352-3026(18)30018-8","article-title":"Ibrutinib, Lenalidomide, and Rituximab in Relapsed or Refractory Mantle Cell Lymphoma (PHILEMON): A Multicentre, Open-Label, Single-Arm, Phase 2 Trial","volume":"5","author":"Jerkeman","year":"2018","journal-title":"Lancet Haematol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1182\/blood-2018-07-859769","article-title":"Five-Year Follow-up of Lenalidomide plus Rituximab as Initial Treatment of Mantle Cell Lymphoma","volume":"132","author":"Ruan","year":"2018","journal-title":"Blood"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1182\/blood-2016-03-704023","article-title":"Lenalidomide-Bendamustine-Rituximab in Patients Older than 65 Years with Untreated Mantle Cell Lymphoma","volume":"128","author":"Kolstad","year":"2016","journal-title":"Blood"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7505","DOI":"10.1200\/JCO.2021.39.15_suppl.7505","article-title":"The Combination of Venetoclax, Lenalidomide, and Rituximab in Patients with Newly Diagnosed Mantle Cell Lymphoma Induces High Response Rates and MRD Undetectability","volume":"39","author":"Phillips","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1182\/blood-2021-149600","article-title":"Rituximab-Lenalidomide(R2) Maintenance Is Superior to Rituximab Maintenance after First Line Immunochemotherapy in Mantle Cell Lymphoma: Results of the MCL R2 Elderly Clinical Trial","volume":"138","author":"Ribrag","year":"2021","journal-title":"Blood"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1182\/blood-2021-145288","article-title":"Impact of Maintenance Arm on Prognostic Value of MRD after Induction Treatment in MCL R2 Elderly Trial, a Mantle Cell Lymphoma Network Study","volume":"138","author":"Delfau","year":"2021","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1093\/annonc\/mdt366","article-title":"Long-Term Follow-up of Lenalidomide in Relapsed\/Refractory Mantle Cell Lymphoma: Subset Analysis of the NHL-003 Study","volume":"24","author":"Zinzani","year":"2013","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/S1470-2045(12)70200-0","article-title":"Lenalidomide in Combination with Rituximab for Patients with Relapsed or Refractory Mantle-Cell Lymphoma: A Phase 1\/2 Clinical Trial","volume":"13","author":"Wang","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1182\/blood-2020-138731","article-title":"Initial Treatment with Lenalidomide Plus Rituximab for Mantle Cell Lymphoma (MCL): 7-Year Analysis from a Multi-Center Phase II Study","volume":"136","author":"Yamshon","year":"2020","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3537","DOI":"10.1182\/blood-2021-147032","article-title":"Phase 1b\/2 Study of Vipor (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Lenalidomide) in Relapsed\/Refractory and Untreated Mantle Cell Lymphoma: Safety, Efficacy, and Molecular Analysis","volume":"138","author":"Melani","year":"2021","journal-title":"Blood"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/bjh.14866","article-title":"Activity of Lenalidomide in Mantle Cell Lymphoma Can Be Explained by NK Cell-Mediated Cytotoxicity","volume":"179","author":"Hagner","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1182\/blood.2019002395","article-title":"Avadomide Monotherapy in Relapsed\/Refractory DLBCL: Safety, Efficacy, and a Predictive Gene Classifier","volume":"135","author":"Carpio","year":"2020","journal-title":"Blood"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1182\/blood-2016-02-698092","article-title":"Targeted Sequencing of Refractory Myeloma Reveals a High Incidence of Mutations in CRBN and Ras Pathway Genes","volume":"128","author":"Mai","year":"2016","journal-title":"Blood"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1182\/blood.2020010452","article-title":"Cereblon Enhancer Methylation and IMiD Resistance in Multiple Myeloma","volume":"138","author":"Haertle","year":"2021","journal-title":"Blood"},{"key":"ref_90","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. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s10637-018-0655-0","article-title":"A Phase 1 Trial of SGN-CD70A in Patients with CD70-Positive Diffuse Large B Cell Lymphoma and Mantle Cell Lymphoma","volume":"37","author":"Phillips","year":"2019","journal-title":"Investig. New Drugs"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4652","DOI":"10.1158\/1078-0432.CCR-20-5039","article-title":"SOX11 Inhibitors Are Cytotoxic in Mantle Cell Lymphoma","volume":"27","author":"Jatiani","year":"2021","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/nrclinonc.2013.46","article-title":"Treating B-Cell Cancer with T Cells Expressing Anti-CD19 Chimeric Antigen Receptors","volume":"10","author":"Kochenderfer","year":"2013","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nature22395","article-title":"Therapeutic T Cell Engineering","volume":"545","author":"Sadelain","year":"2017","journal-title":"Nature"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1111\/bjh.16416","article-title":"Efficacy of R-BAC in Relapsed, Refractory Mantle Cell Lymphoma Post BTK Inhibitor Therapy","volume":"189","author":"McCulloch","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1182\/blood-2020-139063","article-title":"One-Year Follow-up of ZUMA-2, the Multicenter, Registrational Study of KTE-X19 in Patients with Relapsed\/Refractory Mantle Cell Lymphoma","volume":"136","author":"Wang","year":"2020","journal-title":"Blood"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1182\/blood-2021-148626","article-title":"Kte-X19 in Relapsed or Refractory Mantle-Cell Lymphoma, a \u201cReal-Life\u201d Study from the Descar-T Registry and Lysa Group","volume":"138","author":"Herbaux","year":"2021","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1182\/blood-2021-147563","article-title":"Brexucabtagene Autoleucel for Relapsed\/Refractory Mantle Cell Lymphoma: Real World Experience from the US Lymphoma CAR T Consortium","volume":"138","author":"Wang","year":"2021","journal-title":"Blood"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1182\/blood-2020-136158","article-title":"Safety and Preliminary Efficacy in Patients with Relapsed\/Refractory Mantle Cell Lymphoma Receiving Lisocabtagene Maraleucel in Transcend NHL 001","volume":"136","author":"Palomba","year":"2020","journal-title":"Blood"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1182\/blood.2021012634","article-title":"Pembrolizumab for B-Cell Lymphomas Relapsing after or Refractory to CD19-Directed CAR T-Cell Therapy","volume":"139","author":"Chong","year":"2022","journal-title":"Blood"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s40364-021-00294-9","article-title":"The Landscape of Bispecific T Cell Engager in Cancer Treatment","volume":"9","author":"Zhou","year":"2021","journal-title":"Biomark. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1200\/JCO.2014.59.1586","article-title":"Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed\/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study","volume":"34","author":"Goebeler","year":"2016","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1182\/bloodadvances.2019000025","article-title":"Long-Term Outcome of Patients with Relapsed\/Refractory B-Cell Non-Hodgkin Lymphoma Treated with Blinatumomab","volume":"3","author":"Dufner","year":"2019","journal-title":"Blood Adv."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1200\/JCO.21.00931","article-title":"Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study","volume":"40","author":"Budde","year":"2022","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4785","DOI":"10.1158\/1078-0432.CCR-18-0455","article-title":"CD20-TCB with Obinutuzumab Pretreatment as Next-Generation Treatment of Hematologic Malignancies","volume":"24","author":"Bacac","year":"2018","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1056\/NEJMoa1313984","article-title":"Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions","volume":"370","author":"Goede","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1182\/blood-2009-06-225979","article-title":"Increasing the Efficacy of CD20 Antibody Therapy through the Engineering of a New Type II Anti-CD20 Antibody with Enhanced Direct and Immune Effector Cell-Mediated B-Cell Cytotoxicity","volume":"115","author":"Moser","year":"2010","journal-title":"Blood"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.4049\/jimmunol.1301249","article-title":"Glycoengineering of Therapeutic Antibodies Enhances Monocyte\/Macrophage-Mediated Phagocytosis and Cytotoxicity","volume":"192","author":"Herter","year":"2014","journal-title":"J. Immunol. Baltim."},{"key":"ref_109","unstructured":"(2022, May 03). Paper: Glofitamab Step-up Dosing Induces High Response Rates in Patients (Pts) with Relapsed or Refractory (R\/R) Mantle Cell Lymphoma (MCL), Most of Whom Had Failed Prior Bruton\u2019s Tyrosine Kinase Inhibitor (BTKi) Therapy. Available online: https:\/\/ash.confex.com\/ash\/2021\/webprogram\/Paper148949.html."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/S0140-6736(21)00889-8","article-title":"Dose Escalation of Subcutaneous Epcoritamab in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma: An Open-Label, Phase 1\/2 Study","volume":"398","author":"Hutchings","year":"2021","journal-title":"Lancet"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3339","DOI":"10.1182\/bloodadvances.2021006934","article-title":"Survival of Mantle Cell Lymphoma in the Era of Bruton Tyrosine Kinase Inhibitors: A Population-Based Analysis","volume":"6","author":"Di","year":"2022","journal-title":"Blood Adv."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1182\/bloodadvances.2021005715","article-title":"Evolving Frontline Immunochemotherapy for Mantle Cell Lymphoma and the Impact on Survival Outcomes","volume":"6","author":"Castellino","year":"2022","journal-title":"Blood Adv."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/13\/3229\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:41:13Z","timestamp":1760139673000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/13\/3229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,30]]},"references-count":112,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["cancers14133229"],"URL":"https:\/\/doi.org\/10.3390\/cancers14133229","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,30]]}}}