{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:07:07Z","timestamp":1769731627568,"version":"3.49.0"},"reference-count":67,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Veterans Administration","award":["1 I01 BX006101-01A1"],"award-info":[{"award-number":["1 I01 BX006101-01A1"]}]},{"name":"Veterans Administration","award":["P30 CA138313"],"award-info":[{"award-number":["P30 CA138313"]}]},{"name":"MUSC Tissue Biorepository as part of the Hollings Cancer Center at the Medical University of South Carolina","award":["1 I01 BX006101-01A1"],"award-info":[{"award-number":["1 I01 BX006101-01A1"]}]},{"name":"MUSC Tissue Biorepository as part of the Hollings Cancer Center at the Medical University of South Carolina","award":["P30 CA138313"],"award-info":[{"award-number":["P30 CA138313"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>B-cell lymphomas, including Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL), evade CD4+ T-cell immunity through novel HLA class II-associated immunosuppressive mechanisms. Despite expressing surface HLA-DR, these tumors fail to activate antigen-specific CD4+ T cells, independent of co-stimulation or PD-L1 checkpoint inhibition. We identified lymphoma-secreted factors that broadly disrupt HLA class II-mediated antigen presentation in both malignant B cells and dendritic cells (DCs), silencing T-cell responses. This inhibition is allele-independent (affecting DR1, DR4, DR7) but spares HLA class I-mediated CD8+ T-cell recognition, indicating a targeted immune evasion strategy. Biochemical and mass spectrometry (MALDI-MS) analyses revealed unique low-molecular-weight peptides (693\u2013790 Da) in BL cells, absent in normal B cells, which may mediate this suppression. Functional fractionation confirmed bioactive inhibitory fractions in lymphoma lysates, further implicating tumor-intrinsic molecules in immune escape. These findings highlight a previously unrecognized axis of B-cell lymphoma immune evasion, where secreted factors disable HLA class II function across antigen-presenting cells. Therapeutically, neutralizing these immunosuppressive molecules could restore CD4+ T-cell surveillance and enhance immunotherapies in B-cell malignancies. This work underscores the importance of HLA class II dysfunction in lymphoma progression and identifies candidate targets for reversing immune suppression.<\/jats:p>","DOI":"10.3390\/cells14151220","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T10:58:26Z","timestamp":1754564306000},"page":"1220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["B-Cell Lymphomas Secrete Novel Inhibitory Molecules That Disrupt HLA Class II-Mediated CD4+ T-Cell Recognition"],"prefix":"10.3390","volume":"14","author":[{"given":"Jason M.","family":"God","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA"},{"name":"Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shereen","family":"Amria","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA"},{"name":"Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine A.","family":"Cameron","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA"},{"name":"Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lixia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA"},{"name":"Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer R.","family":"Bethard","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6386-9390","authenticated-orcid":false,"given":"Azizul","family":"Haque","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA"},{"name":"Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA"},{"name":"Department of Neurosurgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA"},{"name":"Ralph H. Johnson Veterans Administration Medical Center, 109 Bee St, Charleston, SC 29401, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"156036","DOI":"10.1016\/j.prp.2025.156036","article-title":"B-cell lymphoma: Advances in pathogenesis, diagnosis, and targeted therapies","volume":"271","author":"Patil","year":"2025","journal-title":"Pathol. Res. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Brauge, B., Dessauge, E., Creusat, F., and Tarte, K. (2023). Modeling the crosstalk between malignant B cells and their microenvironment in B-cell lymphomas: Challenges and opportunities. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1288110"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Solares, S., Le\u00f3n, J., and Garc\u00eda-Guti\u00e9rrez, L. (2024). The Functional Interaction Between Epstein\u2013Barr Virus and MYC in the Pathogenesis of Burkitt Lymphoma. Cancers, 16.","DOI":"10.3390\/cancers16244212"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"22","DOI":"10.21037\/aol-21-18","article-title":"Reframing Burkitt lymphoma: Virology not epidemiology defines clinical variants","volume":"5","author":"Rochford","year":"2021","journal-title":"Ann. Lymphoma"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"a034843","DOI":"10.1101\/cshperspect.a034843","article-title":"Non-Hodgkin Lymphomas: Malignancies Arising from Mature B Cells","volume":"11","author":"Shingleton","year":"2020","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.imlet.2023.08.007","article-title":"Immune dysregulation as a leading principle for lymphoma development in diverse immunological backgrounds","volume":"263","author":"Kolijn","year":"2023","journal-title":"Immunol. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"531","DOI":"10.3324\/haematol.2015.139493","article-title":"Role of the tumor microenvironment in mature B-cell lymphoid malignancies","volume":"101","author":"Fowler","year":"2016","journal-title":"Haematologica"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Masnikosa, R., Cvetkovi\u0107, Z., and Piri\u0107, D. (2024). Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111384"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41416-020-01048-4","article-title":"Cytotoxic CD8+ T cells in cancer and cancer immunotherapy","volume":"124","author":"Raskov","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.drudis.2021.01.002","article-title":"Tumor-infiltrating CD8+ T cell antitumor efficacy and exhaustion: Molecular insights","volume":"26","author":"Kumar","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kravtsov, D.S., Erbe, A.K., Sondel, P.M., and Rakhmilevich, A.L. (2022). Roles of CD4+ T cells as mediators of antitumor immunity. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.972021"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s00018-017-2686-7","article-title":"CD4 and CD8 T lymphocyte interplay in controlling tumor growth","volume":"75","author":"Ostroumov","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41568-019-0235-4","article-title":"CD8+ T cell states in human cancer: Insights from single-cell analysis","volume":"20","author":"Thommen","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1186\/s12967-024-05134-6","article-title":"CD8+ T cell-based cancer immunotherapy","volume":"22","author":"Chen","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.trecan.2024.07.009","article-title":"CD4+ T cells in antitumor immunity","volume":"10","author":"Montauti","year":"2024","journal-title":"Trends Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41417-020-0183-x","article-title":"Revisiting the role of CD4+ T cells in cancer immunotherapy\u2014New insights into old paradigms","volume":"28","author":"Tay","year":"2020","journal-title":"Cancer Gene Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"516047","DOI":"10.1155\/2010\/516047","article-title":"Burkitt Lymphoma: Pathogenesis and Immune Evasion","volume":"2010","author":"God","year":"2010","journal-title":"J. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4550","DOI":"10.1073\/pnas.072495599","article-title":"MYC overexpression imposes a nonimmunogenic phenotype on Epstein\u2013Barr virus-infected B cells","volume":"99","author":"Staege","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1111\/imm.12281","article-title":"Disruption of HLA class II antigen presentation in Burkitt lymphoma: Implication of a 47 000 MW acid labile protein in CD4+ T-cell recognition","volume":"142","author":"God","year":"2014","journal-title":"Immunology"},{"key":"ref_21","first-page":"780839","article-title":"HLA Class II Defects in Burkitt Lymphoma: Bryostatin-1-Induced 17 kDa Protein Restores CD4+ T-Cell Recognition","volume":"2011","author":"Hossain","year":"2011","journal-title":"J. Immunol. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1172\/JCI22053","article-title":"Critical role of EBNA1-specific CD4+ T cells in the control of mouse Burkitt lymphoma in vivo","volume":"114","author":"Fu","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1007\/s12094-024-03831-8","article-title":"The evolving tumor-associated adipose tissue microenvironment in breast cancer: From cancer initiation to metastatic outgrowth","volume":"27","author":"Yang","year":"2024","journal-title":"Clin. Transl. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth","volume":"41","author":"Joyce","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/s41423-023-00990-6","article-title":"Dendritic cell subsets in cancer immunity and tumor antigen sensing","volume":"20","author":"Salvi","year":"2023","journal-title":"Cell. Mol. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mazzoccoli, L., and Liu, B. (2024). Dendritic Cells in Shaping Anti-Tumor T Cell Response. Cancers, 16.","DOI":"10.3390\/cancers16122211"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.immuni.2022.04.016","article-title":"Dendritic cells can prime anti-tumor CD8+ T cell responses through major histocompatibility complex cross-dressing","volume":"55","author":"MacNabb","year":"2022","journal-title":"Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jing, H., Gao, Y., Sun, Z., and Liu, S. (2025). Recent advances in novel tumor immunotherapy strategies based on regulating the tumor microenvironment and immune checkpoints. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1529403"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s12943-025-02233-w","article-title":"Extracellular vesicles in tumor immunity: Mechanisms and novel insights","volume":"24","author":"Kuang","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1182\/blood.2024025755","article-title":"IL-10 from tumoral B cells modulates the diffuse large B-cell lymphoma microenvironment and response to immunotherapy","volume":"145","author":"Grijalba","year":"2025","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sinkarevs, S., Strumfs, B., Volkova, S., and Strumfa, I. (2024). Tumour Microenvironment: The General Principles of Pathogenesis and Implications in Diffuse Large B Cell Lymphoma. Cells, 13.","DOI":"10.3390\/cells13121057"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Xiong, J., Chi, H., Yang, G., Zhao, S., Zhang, J., Tran, L.J., Xia, Z., Yang, F., and Tian, G. (2023). Revolutionizing anti-tumor therapy: Unleashing the potential of B cell-derived exosomes. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1188760"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/j.1460-2075.1995.tb06978.x","article-title":"B-cell proliferation and induction of early G1-regulating proteins by Epstein-Barr virus mutants conditional for EBNA2","volume":"14","author":"Kempkes","year":"1995","journal-title":"EMBO J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4543","DOI":"10.4049\/jimmunol.166.7.4543","article-title":"Cysteinylation of MHC Class II Ligands: Peptide Endocytosis and Reduction Within APC Influences T Cell Recognition","volume":"166","author":"Haque","year":"2001","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3109\/10428194.2011.615423","article-title":"Mechanisms regulating enhanced human leukocyte antigen class II-mediated CD4 + T cell recognition of human B-cell lymphoma by resveratrol","volume":"53","author":"Radwan","year":"2011","journal-title":"Leuk. Lymphoma"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1002\/eji.200738100","article-title":"HLA-DM negatively regulates HLA-DR4-restricted collagen pathogenic peptide presentation and T cell recognition","volume":"38","author":"Amria","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1084\/jem.20011853","article-title":"Absence of \u03b3-Interferon\u2013inducible Lysosomal Thiol Reductase in Melanomas Disrupts T Cell Recognition of Select Immunodominant Epitopes","volume":"195","author":"Haque","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6413","DOI":"10.4049\/jimmunol.163.12.6413","article-title":"Role of APC in the Selection of Immunodominant T Cell Epitopes","volume":"163","author":"Ma","year":"1999","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.gene.2009.06.013","article-title":"Identification of NFAT binding sites that mediate stimulation of cathepsin K promoter activity by RANK ligand","volume":"446","author":"Balkan","year":"2009","journal-title":"Gene"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1034\/j.1600-0854.2000.010706.x","article-title":"Endocytic Recycling is Required for the Presentation of an Exogenous Peptide via MHC Class II Molecules","volume":"1","author":"Pathak","year":"2000","journal-title":"Traffic"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.cellimm.2011.08.007","article-title":"Enhancement of HLA class II-restricted CD4+ T cell recognition of human melanoma cells following treatment with bryostatin-1","volume":"271","author":"Zhao","year":"2011","journal-title":"Cell. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1007\/s10495-012-0745-y","article-title":"A possible cross-talk between autophagy and apoptosis in generating an immune response in melanoma","volume":"17","author":"Hossain","year":"2012","journal-title":"Apoptosis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.4049\/jimmunol.1402382","article-title":"Elevation of c-MYC Disrupts HLA Class II\u2013Mediated Immune Recognition of Human B Cell Tumors","volume":"194","author":"God","year":"2015","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0074-7696(04)35004-7","article-title":"Cell-surface peptidases","volume":"235","author":"Mentlein","year":"2004","journal-title":"Int Rev Cytol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3109\/07357900009023066","article-title":"Small Bioactive Peptides and Cell Surface Peptidases in Androgen-Independent Prostate Cancer","volume":"18","author":"Nelson","year":"2000","journal-title":"Cancer Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S1074-7613(00)80176-4","article-title":"Proteolysis in MHC Class II Antigen Presentation","volume":"12","author":"Ploegh","year":"2000","journal-title":"Immunity"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5869","DOI":"10.1038\/onc.2008.273","article-title":"HLA antigen changes in malignant cells: Epigenetic mechanisms and biologic significance","volume":"27","author":"Campoli","year":"2008","journal-title":"Oncogene"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e002899","DOI":"10.1136\/jitc-2021-002899","article-title":"Deregulation of HLA-I in cancer and its central importance for immunotherapy","volume":"9","author":"Hazini","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0014-4835(03)00119-2","article-title":"HLA class II antigen expression in uveal melanoma: Correlation with clinicopathological features","volume":"77","author":"Krishnakumar","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"994","DOI":"10.3390\/biom4040994","article-title":"Proteasome Subtypes and Regulators in the Processing of Antigenic Peptides Presented by Class I Molecules of the Major Histocompatibility Complex","volume":"4","author":"Vigneron","year":"2014","journal-title":"Biomolecules"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41392-021-00658-5","article-title":"Inflammation and tumor progression: Signaling pathways and targeted intervention","volume":"6","author":"Zhao","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e1016700","DOI":"10.1080\/2162402X.2015.1016700","article-title":"Reprogramming the tumor microenvironment: Tumor-induced immunosuppressive factors paralyze T cells","volume":"4","author":"Drake","year":"2015","journal-title":"OncoImmunology"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Wang, D., Cui, Q., Yang, Y.J., Liu, A., Zhang, G., and Yu, J.C. (2022). Application of dendritic cells in tumor immunotherapy and progress in the mechanism of anti-tumor effect of Astragalus polysaccharide (APS) modulating dendritic cells: A review. Biomed. Pharmacother., 155.","DOI":"10.1016\/j.biopha.2022.113541"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Tominaga, M., Uto, T., Fukaya, T., Mitoma, S., Riethmacher, D., Umekita, K., Yamashita, Y., and Sato, K. (2024). Crucial role of dendritic cells in the generation of anti-tumor T-cell responses and immunogenic tumor microenvironment to suppress tumor development. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1200461"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5253","DOI":"10.1038\/s41388-021-01946-8","article-title":"DCision-making in tumors governs T cell anti-tumor immunity","volume":"40","author":"Alfei","year":"2021","journal-title":"Oncogene"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8131","DOI":"10.1007\/s00432-023-04737-8","article-title":"Cancer immune escape: The role of antigen presentation machinery","volume":"149","author":"Kallingal","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.imbio.2014.08.001","article-title":"Hsp90\u2013peptide complexes stimulate antigen presentation through the class II pathway after binding scavenger receptor SREC-I","volume":"219","author":"Murshid","year":"2014","journal-title":"Immunobiology"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kurz, K.S., Ott, M., Kalmbach, S., Steinlein, S., Kalla, C., Horn, H., Ott, G., and Staiger, A.M. (2023). Large B-Cell Lymphomas in the 5th Edition of the WHO-Classification of Haematolymphoid Neoplasms\u2014Updated Classification and New Concepts. Cancers, 15.","DOI":"10.3390\/cancers15082285"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"D\u2019al\u00f2, F., Bellesi, S., Maiolo, E., Alma, E., Bellisario, F., Malafronte, R., Viscovo, M., Campana, F., and Hohaus, S. (2024). Novel Targets and Advanced Therapies in Diffuse Large B Cell Lymphomas. Cancers, 16.","DOI":"10.3390\/cancers16122243"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.3324\/haematol.2017.184192","article-title":"Hide or defend, the two strategies of lymphoma immune evasion: Potential implications for immunotherapy","volume":"103","author":"Houot","year":"2018","journal-title":"Haematologica"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13045-022-01282-8","article-title":"Immunosuppressive cells in cancer: Mechanisms and potential therapeutic targets","volume":"15","author":"Tie","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Petty, A.J., and Yang, Y. (2019). Tumor-Associated Macrophages in Hematologic Malignancies: New Insights and Targeted Therapies. Cells, 8.","DOI":"10.3390\/cells8121526"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Alibrahim, M.N., Gloghini, A., and Carbone, A. (2024). Pathobiological Features and Therapeutic Opportunities Linked to TNF Family Member Expression in Classic Hodgkin Lymphoma. Cancers, 16.","DOI":"10.3390\/cancers16234070"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Melaccio, A., Reale, A., Saltarella, I., Desantis, V., Lamanuzzi, A., Cicco, S., Frassanito, M.A., Vacca, A., and Ria, R. (2022). Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance. J. Clin. Med., 11.","DOI":"10.3390\/jcm11216491"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Lam, H.P.J., Amin, F., Arulogun, S.O., and Gleeson, M. (2025). Nodal Peripheral T-Cell Lymphoma: Therapeutic Challenges and Future Perspectives. Cancers, 17.","DOI":"10.3390\/cancers17071134"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12943-023-01904-w","article-title":"Therapeutic challenges in peripheral T-cell lymphoma","volume":"23","author":"Luan","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1053\/j.seminhematol.2023.12.004","article-title":"Role of the tumor microenvironment in CLL pathogenesis","volume":"61","author":"Stein","year":"2023","journal-title":"Semin. 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