{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:34:47Z","timestamp":1789670087079,"version":"4.0.1"},"reference-count":222,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"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>Immune checkpoints such as PD-1\/PD-L1, CTLA-4, LAG-3, TIM-3, and TIGIT play critical roles in regulating anti-tumor immunity and are exploited by hematological malignancies to evade immune surveillance. While classic Hodgkin lymphoma (HL) demonstrates notable responsiveness to immune checkpoint inhibitors (ICIs), which is attributed to genetic alterations like chromosome 9p24.1 amplification, the responsiveness of non-Hodgkin lymphoma (NHL), acute myeloid leukemia (AML), and multiple myeloma (MM) remain inconsistent and generally modest. In NHL, the heterogeneous immune microenvironment, particularly variations in tumor-infiltrating lymphocytes and PD-L1 expression, drives differential ICI outcomes. AML shows limited responsiveness to monotherapy, but the combination of monotherapy with hypomethylating agents yield encouraging results, particularly in selected patient subsets. Conversely, MM trials have largely failed, potentially due to genetic polymorphisms influencing checkpoint signaling pathways and the inherently immunosuppressive bone marrow microenvironment. Both intrinsic tumor factors (low tumor mutational burden, impaired antigen presentation, IFN-\u03b3 pathway alterations) and extrinsic factors (immunosuppressive cells and alternative checkpoint upregulation) contribute significantly to primary and acquired resistance mechanisms. Future strategies to overcome resistance emphasize combination therapies, such as dual checkpoint blockade, epigenetic modulation, and reprogramming the tumor microenvironment, as well as biomarker-driven patient selection, aiming for precision-based, tailored immunotherapy across hematological malignancies.<\/jats:p>","DOI":"10.3390\/cancers17142292","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:38:27Z","timestamp":1752140307000},"page":"2292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Immune Checkpoint Molecules in Hodgkin Lymphoma and Other Hematological Malignancies"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9390-5645","authenticated-orcid":false,"given":"Mohamed Nazem","family":"Alibrahim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2211-639X","authenticated-orcid":false,"given":"Antonino","family":"Carbone","sequence":"additional","affiliation":[{"name":"Centro di Riferimento Oncologico Aviano, IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2086-3084","authenticated-orcid":false,"given":"Noor","family":"Alsaleh","sequence":"additional","affiliation":[{"name":"Noor Alsaleh Faculty of Medicine, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7226-1942","authenticated-orcid":false,"given":"Annunziata","family":"Gloghini","sequence":"additional","affiliation":[{"name":"Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1084\/jem.183.6.2533","article-title":"CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells","volume":"183","author":"Krummel","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/85330","article-title":"PD-L2 is a second ligand for PD-1 and inhibits T cell activation","volume":"2","author":"Latchman","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1084\/jem.183.6.2541","article-title":"CTLA-4 ligation blocks CD28-dependent T cell activation","volume":"183","author":"Walunas","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1002\/cac2.12587","article-title":"Advances and clinical applications of immune checkpoint inhibitors in hematological malignancies","volume":"44","author":"Sun","year":"2024","journal-title":"Cancer Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/nm730","article-title":"Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion","volume":"8","author":"Dong","year":"2002","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1084\/jem.192.7.1027","article-title":"Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation","volume":"192","author":"Freeman","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1411087","article-title":"PD-1 blockade with nivolumab in relapsed or refractory Hodgkin\u2019s lymphoma","volume":"372","author":"Ansell","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1200\/JCO.2014.59.4358","article-title":"Immune checkpoint blockade in cancer therapy","volume":"33","author":"Postow","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_11","first-page":"5019","article-title":"The 2008 WHO classification of lymphoid neoplasms and beyond: Evolving concepts and practical applications","volume":"117","author":"Campo","year":"2011","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/S1470-2045(16)30167-X","article-title":"Nivolumab for classical Hodgkin\u2019s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: A multicentre, multicohort, single-arm phase 2 trial","volume":"17","author":"Timmerman","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Tsumura, A., Levis, D., and Tuscano, J.M. (2023). Checkpoint inhibition in hematologic malignancies. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1288172"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5272","DOI":"10.1182\/bloodadvances.2023010254","article-title":"Nivolumab combined with brentuximab vedotin for R\/R primary mediastinal large B-cell lymphoma: A 3-year follow-up","volume":"7","author":"Zinzani","year":"2023","journal-title":"Blood Adv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1158\/2159-8290.CD-18-0774","article-title":"Efficacy, safety, and biomarkers of response to azacitidine and nivolumab in relapsed\/refractory acute myeloid leukemia: A nonrandomized, open-label, phase II study","volume":"9","author":"Daver","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e459","DOI":"10.1016\/S2352-3026(19)30110-3","article-title":"Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): A randomised, open-label, phase 3 trial","volume":"6","author":"Mateos","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/S0140-6736(09)60221-X","article-title":"Multiple myeloma","volume":"374","author":"Raab","year":"2009","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1146\/annurev.immunol.14.1.233","article-title":"CD28\/B7 system of T cell costimulation","volume":"14","author":"Lenschow","year":"1996","journal-title":"Annu. Rev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"224","DOI":"10.2174\/187152212802001875","article-title":"Modulating co-stimulation during antigen presentation to enhance cancer immunotherapy","volume":"12","author":"Liechtenstein","year":"2012","journal-title":"Immunol. Endocr. Metab. Agents Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nri3405","article-title":"Molecular mechanisms of T cell co-stimulation and co-inhibition","volume":"13","author":"Chen","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1600-065X.2009.00770.x","article-title":"CD28 and CTLA-4 coreceptor expression and signal transduction","volume":"229","author":"Rudd","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12943-024-02023-w","article-title":"Regulatory mechanisms of PD-1\/PD-L1 in cancers","volume":"23","author":"Lin","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Shibru, B., Fey, K., Fricke, S., Blaudszun, A.-R., F\u00fcrst, F., Weise, M., Seiffert, S., Weyh, M.K., K\u00f6hl, U., and Sack, U. (2021). Detection of immune checkpoint receptors\u2013a current challenge in clinical flow cytometry. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.694055"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5309","DOI":"10.1016\/j.cell.2021.09.020","article-title":"Hallmarks of response, resistance, and toxicity to immune checkpoint blockade","volume":"184","author":"Morad","year":"2021","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"205","DOI":"10.4049\/jimmunol.1601464","article-title":"Conserved region C functions to regulate PD-1 expression and subsequent CD8 T cell memory","volume":"198","author":"Bally","year":"2017","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4545","DOI":"10.4049\/jimmunol.1402550","article-title":"NF-\u03baB regulates PD-1 expression in macrophages","volume":"194","author":"Bally","year":"2015","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4832","DOI":"10.4049\/jimmunol.181.7.4832","article-title":"NFATc1 regulates PD-1 expression upon T cell activation","volume":"181","author":"Oestreich","year":"2008","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4876","DOI":"10.4049\/jimmunol.1302750","article-title":"STAT3, STAT4, NFATc1, and CTCF regulate PD-1 through multiple novel regulatory regions in murine T cells","volume":"192","author":"Austin","year":"2014","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1093\/intimm\/8.5.765","article-title":"Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes","volume":"8","author":"Agata","year":"1996","journal-title":"Int. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.coi.2010.03.007","article-title":"Role of PD-1 in regulating acute infections","volume":"22","author":"Brown","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.immuni.2011.06.015","article-title":"Chronic virus infection enforces demethylation of the locus that encodes PD-1 in antigen-specific CD8+ T cells","volume":"35","author":"Youngblood","year":"2011","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8934","DOI":"10.1128\/JVI.00798-16","article-title":"Demethylation of the PD-1 promoter is imprinted during the effector phase of CD8 T cell exhaustion","volume":"90","author":"Ahn","year":"2016","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.4049\/jimmunol.1300675","article-title":"Type I IFN induces binding of STAT1 to Bcl6: Divergent roles of STAT family transcription factors in the T follicular helper cell genetic program","volume":"192","author":"Nakayamada","year":"2014","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bao, S., Jiang, X., Jin, S., Tu, P., and Lu, J. (2021). TGF-\u03b21 induces immune escape by enhancing PD-1 and CTLA-4 expression on T lymphocytes in hepatocellular carcinoma. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.694145"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nature04444","article-title":"Restoring function in exhausted CD8 T cells during chronic viral infection","volume":"439","author":"Barber","year":"2006","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41591-018-0337-7","article-title":"Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma","volume":"25","author":"Cloughesy","year":"2019","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2106307","DOI":"10.1002\/adma.202106307","article-title":"Self-blockade of PD-L1 with bacteria-derived outer-membrane vesicle for enhanced cancer immunotherapy","volume":"34","author":"Pan","year":"2022","journal-title":"Adv. Mater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1097\/PPO.0000000000000061","article-title":"Inducible expression of B7-H1 (PD-L1) and its selective role in tumor site immune modulation","volume":"20","author":"Sanmamed","year":"2014","journal-title":"Cancer J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/ni1443","article-title":"The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection","volume":"8","author":"Sharpe","year":"2007","journal-title":"Nat. Immunol."},{"key":"ref_40","first-page":"656340","article-title":"Programmed death ligand 2 in cancer-induced immune suppression","volume":"2012","author":"Rozali","year":"2012","journal-title":"J. Immunol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-020-01165-x","article-title":"CCL2-CCR2 axis recruits tumor associated macrophages to induce immune evasion through PD-1 signaling in esophageal carcinogenesis","volume":"19","author":"Yang","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.molmed.2014.10.009","article-title":"Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway","volume":"21","author":"Ohaegbulam","year":"2015","journal-title":"Trends Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12967-014-0373-0","article-title":"PD-1\/PD-L1 pathway in non-small-cell lung cancer and its relation with EGFR mutation","volume":"13","author":"Ji","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4574","DOI":"10.4049\/jimmunol.171.9.4574","article-title":"Absence of programmed death receptor 1 alters thymic development and enhances generation of CD4\/CD8 double-negative TCR-transgenic T cells","volume":"171","author":"Blank","year":"2003","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1097\/01.pas.0000209855.28282.ce","article-title":"Programmed death-1 (PD-1) is a marker of germinal center-associated T cells and angioimmunoblastic T-cell lymphoma","volume":"30","author":"Dorfman","year":"2006","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1593\/neo.05733","article-title":"The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: Correlation with important high-risk prognostic factors","volume":"8","author":"Ghebeh","year":"2006","journal-title":"Neoplasia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1002\/ijc.23042","article-title":"Augmented expression of programmed death-1 in both neoplastic and non-neoplastic CD4+ T-cells in adult T-cell leukemia\/lymphoma","volume":"121","author":"Shimauchi","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_48","first-page":"3220","article-title":"PD-1\u2013PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma","volume":"111","author":"Yamamoto","year":"2008","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_49","first-page":"4501","article-title":"Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia","volume":"117","author":"Zhou","year":"2011","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Christiansson, L., S\u00f6derlund, S., Svensson, E., Mustjoki, S., Bengtsson, M., Simonsson, B., Olsson-Str\u00f6mberg, U., and Loskog, A.S. (2013). Increased level of myeloid-derived suppressor cells, programmed death receptor ligand 1\/programmed death receptor 1, and soluble CD25 in Sokal high risk chronic myeloid leukemia. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055818"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/35069112","article-title":"Structural basis for co-stimulation by the human CTLA-4\/B7-2 complex","volume":"410","author":"Schwartz","year":"2001","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/35069118","article-title":"Crystal structure of the B7-1\/CTLA-4 complex that inhibits human immune responses","volume":"410","author":"Stamper","year":"2001","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S1074-7613(02)00362-X","article-title":"The interaction properties of costimulatory molecules revisited","volume":"17","author":"Collins","year":"2002","journal-title":"Immunity"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/nri3108","article-title":"The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses","volume":"11","author":"Walker","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.immuni.2004.06.017","article-title":"B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse","volume":"21","author":"Egen","year":"2004","journal-title":"Immunity"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.immuni.2010.09.006","article-title":"Spatiotemporal basis of CTLA-4 costimulatory molecule-mediated negative regulation of T cell activation","volume":"33","author":"Yokosuka","year":"2010","journal-title":"Immunity"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1126\/science.1202947","article-title":"Trans-endocytosis of CD80 and CD86: A molecular basis for the cell-extrinsic function of CTLA-4","volume":"332","author":"Qureshi","year":"2011","journal-title":"Science"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"101298","DOI":"10.1016\/j.smim.2019.101298","article-title":"CTLA-4 (CD152): A versatile receptor for immune-based therapy","volume":"42","author":"Lingel","year":"2019","journal-title":"Semin. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S1074-7613(00)80346-5","article-title":"Tyrosine phosphorylation controls internalization of CTLA-4 by regulating its interaction with clathrin-associated adaptor complex AP-2","volume":"6","author":"Shiratori","year":"1997","journal-title":"Immunity"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"144","DOI":"10.4049\/jimmunol.159.1.144","article-title":"Interaction of CTLA-4 with the clathrin-associated protein AP50 results in ligand-independent endocytosis that limits cell surface expression","volume":"159","author":"Chuang","year":"1997","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1126\/science.aaa1663","article-title":"Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy","volume":"349","author":"Lo","year":"2015","journal-title":"Science"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1128\/MCB.01331-13","article-title":"Rab8 binding to immune cell-specific adaptor LAX facilitates formation of trans-Golgi network-proximal CTLA-4 vesicles for surface expression","volume":"34","author":"Banton","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/COC.0000000000000239","article-title":"CTLA-4 and PD-1 pathways: Similarities, differences, and implications of their inhibition","volume":"39","author":"Buchbinder","year":"2016","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1038\/leu.2015.357","article-title":"Recurrent activating mutations of CD28 in peripheral T-cell lymphomas","volume":"30","author":"Rohr","year":"2016","journal-title":"Leukemia"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1038\/ng.3415","article-title":"Integrated molecular analysis of adult T cell leukemia\/lymphoma","volume":"47","author":"Kataoka","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1126\/science.271.5256.1734","article-title":"Enhancement of antitumor immunity by CTLA-4 blockade","volume":"271","author":"Leach","year":"1996","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1084\/jem.190.3.355","article-title":"Combination immunotherapy of B16 melanoma using anti\u2013cytotoxic T lymphocyte\u2013associated antigen 4 (CTLA-4) and granulocyte\/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation","volume":"190","author":"Hurwitz","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1084\/jem.194.4.481","article-title":"Elucidating the autoimmune and antitumor effector mechanisms of a treatment based on cytotoxic T lymphocyte antigen-4 blockade in combination with a B16 melanoma vaccine: Comparison of prophylaxis and therapy","volume":"194","author":"Sutmuller","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"E4223","DOI":"10.1073\/pnas.1617941114","article-title":"Structural basis for cancer immunotherapy by the first-in-class checkpoint inhibitor ipilimumab","volume":"114","author":"Ramagopal","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","first-page":"505","article-title":"Tremelimumab, a fully human monoclonal IgG2 antibody against CTLA4 for the potential treatment of cancer","volume":"9","author":"Tarhini","year":"2007","journal-title":"Curr. Opin. Mol. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrclinonc.2016.58","article-title":"Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination","volume":"13","author":"Boutros","year":"2016","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_72","first-page":"58","article-title":"CTLA-4: A moving target in immunotherapy","volume":"131","author":"Rowshanravan","year":"2018","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"238ra270","DOI":"10.1126\/scitranslmed.3008211","article-title":"Improved survival with T cell clonotype stability after anti-CTLA-4 treatment in cancer patients","volume":"6","author":"Cha","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1158\/0008-5472.CAN-16-2324","article-title":"Immune toxicities elicted by CTLA-4 blockade in cancer patients are associated with early diversification of the T-cell repertoire","volume":"77","author":"Oh","year":"2017","journal-title":"Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"11919","DOI":"10.1073\/pnas.1611421113","article-title":"Clonal expansion of CD8 T cells in the systemic circulation precedes development of ipilimumab-induced toxicities","volume":"113","author":"Subudhi","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"eabg8693","DOI":"10.1126\/scitranslmed.abg8693","article-title":"Dual targeting of CTLA-4 and CD47 on Treg cells promotes immunity against solid tumors","volume":"13","author":"Zhang","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"106221","DOI":"10.1016\/j.intimp.2020.106221","article-title":"CTLA-4: From mechanism to autoimmune therapy","volume":"80","author":"Hosseini","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/nm.3746","article-title":"Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations","volume":"20","author":"Schubert","year":"2014","journal-title":"Nat. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1126\/science.1255904","article-title":"Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4","volume":"345","author":"Kuehn","year":"2014","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.ajhg.2012.04.015","article-title":"Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity","volume":"90","author":"Tampella","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.immuni.2022.03.013","article-title":"Binding of LAG-3 to stable peptide-MHC class II limits T cell function and suppresses autoimmunity and anti-cancer immunity","volume":"55","author":"Maruhashi","year":"2022","journal-title":"Immunity"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1084\/jem.171.5.1393","article-title":"LAG-3, a novel lymphocyte activation gene closely related to CD4","volume":"171","author":"Triebel","year":"1990","journal-title":"J. Exp. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1002\/eji.1830250949","article-title":"CD4\/major histocompatibility complex class II interaction analyzed with CD4-and lymphocyte activation gene-3 (LAG-3)-Ig fusion proteins","volume":"25","author":"Huard","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5282","DOI":"10.3390\/ijms22105282","article-title":"Understanding LAG-3 signaling","volume":"22","author":"Chocarro","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1002\/eji.1830260533","article-title":"T cell major histocompatibility complex class II molecules down-regulate CD4+ T cell clone responses following LAG-3 binding","volume":"26","author":"Huard","year":"1996","journal-title":"Eur. J. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/s40265-022-01723-1","article-title":"Nivolumab plus relatlimab: First approval","volume":"82","author":"Paik","year":"2022","journal-title":"Drugs"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1056\/NEJMoa2109970","article-title":"Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma","volume":"386","author":"Tawbi","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13567-018-0543-9","article-title":"Cooperation of PD-1 and LAG-3 in the exhaustion of CD4+ and CD8+ T cells during bovine leukemia virus infection","volume":"49","author":"Okagawa","year":"2018","journal-title":"Vet. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1158\/2326-6066.CIR-14-0150","article-title":"Galectin-3 shapes antitumor immune responses by suppressing CD8+ T cells via LAG-3 and inhibiting expansion of plasmacytoid dendritic cells","volume":"3","author":"Kouo","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.cell.2018.11.010","article-title":"Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3","volume":"176","author":"Wang","year":"2019","journal-title":"Cell"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/nature13848","article-title":"CEACAM1 regulates TIM-3-mediated tolerance and exhaustion","volume":"517","author":"Huang","year":"2015","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1080\/14737140.2021.1865814","article-title":"TIM-3 pathway dysregulation and targeting in cancer","volume":"21","author":"Zeidan","year":"2021","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1038\/ni.2376","article-title":"Tumor-infiltrating DCs suppress nucleic acid\u2013mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1","volume":"13","author":"Chiba","year":"2012","journal-title":"Nat. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1084\/jem.20100643","article-title":"Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity","volume":"207","author":"Sakuishi","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"10501","DOI":"10.1038\/ncomms10501","article-title":"Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints","volume":"7","author":"Koyama","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s13045-023-01499-1","article-title":"Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy","volume":"16","author":"Cai","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/ni.1674","article-title":"The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells","volume":"10","author":"Yu","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1002\/eji.201041136","article-title":"Vstm3 is a member of the CD28 family and an important modulator of T-cell function","volume":"41","author":"Levin","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.immuni.2015.01.010","article-title":"Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack","volume":"42","author":"Gur","year":"2015","journal-title":"Immunity"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1003466","article-title":"Improved survival with ipilimumab in patients with metastatic melanoma","volume":"363","author":"Hodi","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1084\/jem.20150785","article-title":"Identification of CD112R as a novel checkpoint for human T cells","volume":"213","author":"Zhu","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.clim.2017.08.021","article-title":"CD8+ T cells expressing both PD-1 and TIGIT but not CD226 are dysfunctional in acute myeloid leukemia (AML) patients","volume":"190","author":"Wang","year":"2018","journal-title":"Clin. Immunol."},{"key":"ref_103","first-page":"1689","article-title":"TIGIT immune checkpoint blockade restores CD8+ T-cell immunity against multiple myeloma","volume":"132","author":"Guillerey","year":"2018","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Jin, S., Zhang, Y., Zhou, F., Chen, X., Sheng, J., and Zhang, J. (2022). TIGIT: A promising target to overcome the barrier of immunotherapy in hematological malignancies. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1091782"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10238-022-00817-0","article-title":"TIGIT axis: Novel immune checkpoints in anti-leukemia immunity","volume":"23","author":"Qiu","year":"2023","journal-title":"Clin. Exp. Med."},{"key":"ref_106","first-page":"100239","article-title":"Advances in the management of non-small cell lung cancer (NSCLC): A new practice changing data from asco 2020 annual meeting","volume":"25","author":"Houssaini","year":"2020","journal-title":"Cancer Treat. Res. Commun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e008591","DOI":"10.1136\/jitc-2023-008591","article-title":"Chronic immune-related adverse events arising from immune checkpoint inhibitors: An update","volume":"12","author":"Fletcher","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1001\/jamaoncol.2021.0051","article-title":"Chronic immune-related adverse events following adjuvant anti\u2013PD-1 therapy for high-risk resected melanoma","volume":"7","author":"Patrinely","year":"2021","journal-title":"JAMA Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e006500","DOI":"10.1136\/jitc-2022-006500","article-title":"Chronic immune-related adverse events in patients with cancer receiving immune checkpoint inhibitors: A systematic review","volume":"11","author":"Barron","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1158\/2326-6066.CIR-18-0717","article-title":"Anti\u2013PD-1\u2013induced Pneumonitis is associated with persistent imaging abnormalities in melanoma patients","volume":"7","author":"Johnson","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1200\/JCO.2016.66.4482","article-title":"PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome","volume":"34","author":"Roemer","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.semradonc.2024.11.002","article-title":"Rising to the Top: How Immune-Checkpoint Inhibitors are Changing the Landscape of Treatment for Classic Hodgkin Lymphoma","volume":"35","author":"Lynch","year":"2025","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1200\/JCO.2016.72.1316","article-title":"Phase II study of the efficacy and safety of pembrolizumab for relapsed\/refractory classic Hodgkin lymphoma","volume":"35","author":"Chen","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1182\/blood.2022019386","article-title":"Five-year follow-up of KEYNOTE-087: Pembrolizumab monotherapy for relapsed\/refractory classical Hodgkin lymphoma","volume":"142","author":"Armand","year":"2023","journal-title":"Blood"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"6266","DOI":"10.1182\/bloodadvances.2023010334","article-title":"Nivolumab for relapsed\/refractory classical Hodgkin lymphoma: 5-year survival from the pivotal phase 2 CheckMate 205 study","volume":"7","author":"Ansell","year":"2023","journal-title":"Blood Adv."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/S1470-2045(21)00005-X","article-title":"Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): An interim analysis of a multicentre, randomised, open-label, phase 3 study","volume":"22","author":"Kuruvilla","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/bjh.15639","article-title":"The role of transplantation in Hodgkin lymphoma","volume":"184","author":"Broccoli","year":"2019","journal-title":"Br. J. Haematol."},{"key":"ref_118","first-page":"427","article-title":"Brentuximab vedotin in combination with nivolumab in relapsed or refractory Hodgkin lymphoma: 3-year study results","volume":"138","author":"Advani","year":"2021","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_119","first-page":"2075","article-title":"Nivolumab and brentuximab vedotin with or without bendamustine for R\/R Hodgkin lymphoma in children, adolescents, and young adults","volume":"141","author":"Leblanc","year":"2023","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_120","first-page":"3605","article-title":"Response-adapted anti-PD-1\u2013based salvage therapy for Hodgkin lymphoma with nivolumab alone or in combination with ICE","volume":"139","author":"Mei","year":"2022","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1001\/jamaoncol.2022.7975","article-title":"Pembrolizumab added to ifosfamide, carboplatin, and etoposide chemotherapy for relapsed or refractory classic Hodgkin lymphoma: A multi-institutional phase 2 investigator-initiated nonrandomized clinical trial","volume":"9","author":"Bryan","year":"2023","journal-title":"JAMA Oncol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1097\/01.HS9.0000890964.54059.2c","article-title":"T099: High efficacy and durability of second-line therapy with pembrolizumab, gemcitabine, vinorelbine, and liposomal doxorubicin in the phase II study for relapsed and refractory Hodgkin lymphoma","volume":"6","author":"Moskowitz","year":"2022","journal-title":"HemaSphere"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1001\/jamaoncol.2020.0750","article-title":"Efficacy of nivolumab and AVD in early-stage unfavorable classic Hodgkin lymphoma: The randomized phase 2 German Hodgkin Study Group NIVAHL trial","volume":"6","author":"Goergen","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1182\/blood-2022-163787","article-title":"Pembrolizumab and chemotherapy in newly-diagnosed, early unfavorable or advanced stage classic Hodgkin lymphoma: The phase 2 Keynote-C11 study","volume":"140","author":"Advani","year":"2022","journal-title":"Blood"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Herrera, A.F., LeBlanc, M.L., Castellino, S.M., Li, H., Rutherford, S.C., Evens, A.M., Davison, K., Punnett, A., Hodgson, D.C., and Parsons, S.K. (2023, January 2\u20136). SWOG S1826, a randomized study of nivolumab (N)-AVD versus brentuximab vedotin (BV)-AVD in advanced stage (AS) classic Hodgkin lymphoma (HL). Proceedings of the 2023 ASCO Annual Meeting, Chicago, IL, USA.","DOI":"10.1200\/JCO.2023.41.17_suppl.LBA4"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1158\/1078-0432.CCR-21-2023","article-title":"Tislelizumab for relapsed\/refractory classical Hodgkin lymphoma: 3-year follow-up and correlative biomarker analysis","volume":"28","author":"Song","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_127","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_128","doi-asserted-by":"crossref","first-page":"6446","DOI":"10.1158\/1078-0432.CCR-09-1339","article-title":"Phase I study of ipilimumab, an anti\u2013CTLA-4 monoclonal antibody, in patients with relapsed and refractory B-cell non\u2013Hodgkin lymphoma","volume":"15","author":"Ansell","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"7004","DOI":"10.1158\/1078-0432.CCR-19-0438","article-title":"A phase I study of the combination of rituximab and ipilimumab in patients with relapsed\/refractory B-cell lymphoma","volume":"25","author":"Tuscano","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/s41375-020-0939-1","article-title":"A phase 1b study of dual PD-1 and CTLA-4 or KIR blockade in patients with relapsed\/refractory lymphoid malignancies","volume":"35","author":"Armand","year":"2021","journal-title":"Leukemia"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1200\/JCO.18.00766","article-title":"Nivolumab for relapsed\/refractory diffuse large B-cell lymphoma in patients ineligible for or having failed autologous transplantation: A single-arm, phase II study","volume":"37","author":"Ansell","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_132","first-page":"637","article-title":"Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed\/refractory follicular lymphoma","volume":"137","author":"Armand","year":"2021","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Nowakowski, G.S., Willenbacher, W., Greil, R., Larsen, T.S., Patel, K., J\u00e4ger, U., Manges, R.F., Trumper, L.H., Haioun, C., and Everaus, H. (June, January 31). Safety and efficacy of PD-L1 inhibitor durvalumab with R-CHOP or R2-CHOP in subjects with previously untreated, high-risk DLBCL. Proceedings of the 2019 ASCO Annual Meeting, Chicago, IL, USA.","DOI":"10.1200\/JCO.2019.37.15_suppl.7520"},{"key":"ref_134","first-page":"141","article-title":"Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma: Final analysis of KEYNOTE-170","volume":"142","author":"Zinzani","year":"2023","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1200\/JCO.19.01492","article-title":"Nivolumab combined with brentuximab vedotin for relapsed\/refractory primary mediastinal large B-cell lymphoma: Efficacy and safety from the phase II CheckMate 436 study","volume":"37","author":"Zinzani","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"5855","DOI":"10.1182\/bloodadvances.2024013277","article-title":"Magrolimab plus rituximab in relapsed\/refractory indolent non-Hodgkin lymphoma: 3-year follow-up of a phase 1\/2 trial","volume":"8","author":"Mehta","year":"2024","journal-title":"Blood Adv."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3560","DOI":"10.1182\/blood-2021-153683","article-title":"CD47-blocker TTI-622 shows single-agent activity in patients with advanced relapsed or refractory lymphoma: Update from the ongoing first-in-human dose escalation study","volume":"138","author":"Patel","year":"2021","journal-title":"Blood"},{"key":"ref_138","first-page":"2193","article-title":"Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma","volume":"126","author":"Kiyasu","year":"2015","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_139","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_140","first-page":"3071","article-title":"PD-1 blockade with nivolumab in relapsed\/refractory primary central nervous system and testicular lymphoma","volume":"129","author":"Nayak","year":"2017","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_141","first-page":"2754","article-title":"Avelumab for the treatment of relapsed or refractory extranodal NK\/T-cell lymphoma: An open-label phase 2 study","volume":"136","author":"Kim","year":"2020","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41392-021-00768-0","article-title":"Sintilimab for relapsed\/refractory extranodal NK\/T cell lymphoma: A multicenter, single-arm, phase 2 trial (ORIENT-4)","volume":"6","author":"Tao","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/s41408-021-00539-8","article-title":"Obinutuzumab-atezolizumab-lenalidomide for the treatment of patients with relapsed\/refractory follicular lymphoma: Final analysis of a Phase Ib\/II trial","volume":"11","author":"Morschhauser","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1182\/blood-2018-99-116745","article-title":"Efficacy and toxicity of JCAR014 in combination with durvalumab for the treatment of patients with relapsed\/refractory aggressive B-cell non-Hodgkin lymphoma","volume":"132","author":"Hirayama","year":"2018","journal-title":"Blood"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"J\u00e4ger, U., Worel, N., McGuirk, J., Riedell, P.A., Fleury, I., Borchmann, P., Du, Y., Abdelhady, A.M., Han, X., and Martinez-Prieto, M. (2021, January 11\u201314). Safety and efficacy of tisagenlecleucel (tisa-cel) plus pembrolizumab (pembro) in patients (pts) with relapsed\/refractory diffuse large B-cell lymphoma (r\/r DLBCL): Updated analysis of the phase 1b PORTIA study. Proceedings of the 2021 ASH Annual Meeting, Atlanta, GA, USA.","DOI":"10.1200\/JCO.2021.39.15_suppl.e19537"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"CT055","DOI":"10.1158\/1538-7445.AM2020-CT055","article-title":"Abstract CT055: Phase 1\/2 primary analysis of ZUMA-6: Axicabtagene ciloleucel (Axi-Cel) in combination with atezolizumab (Atezo) for the treatment of patients (Pts) with refractory diffuse large B cell lymphoma (DLBCL)","volume":"80","author":"Jacobson","year":"2020","journal-title":"Cancer Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"4198","DOI":"10.1182\/blood-2018-99-119502","article-title":"Sequential anti-CD19 directed chimeric antigen receptor modified T-cell therapy (CART19) and PD-1 blockade with pembrolizumab in patients with relapsed or refractory B-cell non-Hodgkin lymphomas","volume":"132","author":"Chong","year":"2018","journal-title":"Blood"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Osborne, W., Marzolini, M., Tholouli, E., Ramakrishnan, A., Bachier, C.R., McSweeney, P.A., Irvine, D., Zhang, M., Al-Hajj, M.A., and Pule, M. (2020, January 29\u201331). Phase I Alexander study of AUTO3, the first CD19\/22 dual targeting CAR T cell therapy, with pembrolizumab in patients with relapsed\/refractory (r\/r) DLBCL. Proceedings of the 2020 ASCO Annual Meeting, Virtual Meeting.","DOI":"10.1016\/j.annonc.2020.08.008"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1182\/blood.V128.22.183.183","article-title":"A phase 1 study of nivolumab in combination with ipilimumab for relapsed or refractory hematologic malignancies (CheckMate 039)","volume":"128","author":"Ansell","year":"2016","journal-title":"Blood"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Witzig, T.E., Maddocks, K.J., De Vos, S., Lyons, R.M., Edenfield, W.J., Sharman, J.P., Vose, J., Yimer, H.A., Wei, H., and Chan, E.M. (2019, January 7\u201310). Phase 1\/2 trial of acalabrutinib plus pembrolizumab (Pem) in relapsed\/refractory (r\/r) diffuse large B-cell lymphoma (DLBCL). Proceedings of the 2019 ASH Annual Meeting, Orlando, FL, USA.","DOI":"10.1200\/JCO.2019.37.15_suppl.7519"},{"key":"ref_151","first-page":"e1662","article-title":"Durvalumab as monotherapy and in combination therapy in patients with lymphoma or chronic lymphocytic leukemia: The FUSION NHL 001 trial","volume":"6","author":"Casulo","year":"2023","journal-title":"Cancer Rep."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1182\/bloodadvances.2021005872","article-title":"Pembrolizumab plus dinaciclib in patients with hematologic malignancies: The phase 1b KEYNOTE-155 study","volume":"6","author":"Gregory","year":"2022","journal-title":"Blood Adv."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/ajh.25659","article-title":"Safety and activity of ibrutinib in combination with durvalumab in patients with relapsed or refractory follicular lymphoma or diffuse large B-cell lymphoma","volume":"95","author":"Herrera","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1016\/S2352-3026(18)30217-5","article-title":"Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: A phase 1\/2a study","volume":"6","author":"Younes","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1038\/s41375-025-02566-x","article-title":"Immune checkpoints regulate acute myeloid leukemia stem cells","volume":"39","author":"Reinhardt","year":"2025","journal-title":"Leukemia"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1038\/s41375-019-0441-9","article-title":"CD8+ T cells expand stem and progenitor cells in favorable but not adverse risk acute myeloid leukemia","volume":"33","author":"Radpour","year":"2019","journal-title":"Leukemia"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Radpour, R., Stucki, M., Riether, C., and Ochsenbein, A.F. (2021). Epigenetic silencing of immune-checkpoint receptors in bone marrow-infiltrating T cells in acute myeloid leukemia. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.663406"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Soltani, M., Vosoughi, M., Ganjalikhani-Hakemi, M., Shapoorian, H., Beshkar, P., Eskandari, N., and Ghezelbash, B. (2023). PD-1\/PD-L1 Interaction Regulates BCL2, KI67, BAX, and CASP3, Altering Proliferation, Survival, and Apoptosis in Acute Myeloid Leukemia. Iran. J. Allergy Asthma Immunol., 22.","DOI":"10.18502\/ijaai.v22i5.13998"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Soltani, M., Ghanadian, M., Ghezelbash, B., Shokouhi, A., Zamyatnin Jr, A.A., Bazhin, A.V., and Ganjalikhani-Hakemi, M. (2023). PD-L1 stimulation can promote proliferation and survival of leukemic cells by influencing glucose and fatty acid metabolism in acute myeloid leukemia. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-10947-7"},{"key":"ref_160","first-page":"999","article-title":"High PD-L1 expression drives glycolysis via an Akt\/mTOR\/HIF-1\u03b1 axis in acute myeloid leukemia","volume":"43","author":"Ma","year":"2020","journal-title":"Oncol. Rep."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.stem.2015.07.011","article-title":"A TIM-3\/Gal-9 autocrine stimulatory loop drives self-renewal of human myeloid leukemia stem cells and leukemic progression","volume":"17","author":"Kikushige","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Wang, Z., Chen, J., Wang, M., Zhang, L., and Yu, L. (2021). One stone, two birds: The roles of Tim-3 in acute myeloid leukemia. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.618710"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Pophali, P., Varela, J.C., and Rosenblatt, J. (2024). Immune checkpoint blockade in hematological malignancies: Current state and future potential. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1323914"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.1158\/1078-0432.CCR-07-4079","article-title":"Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies","volume":"14","author":"Berger","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1182\/blood.V128.22.345.345","article-title":"Pembrolizumab, a PD-1 inhibitor, in patients with myelodysplastic syndrome (MDS) after failure of hypomethylating agent treatment","volume":"128","author":"Tallman","year":"2016","journal-title":"Blood"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1158\/1078-0432.CCR-17-3763","article-title":"A multi-center phase I trial of ipilimumab in patients with myelodysplastic syndromes following hypomethylating agent failure","volume":"24","author":"Zeidan","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1056\/NEJMoa1601202","article-title":"Ipilimumab for patients with relapse after allogeneic transplantation","volume":"375","author":"Davids","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1182\/blood.2022017686","article-title":"Ipilimumab plus decitabine for patients with MDS or AML in posttransplant or transplant-na\u00efve settings","volume":"141","author":"Garcia","year":"2023","journal-title":"Blood"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1158\/2643-3230.BCD-21-0070","article-title":"Phase II trial of pembrolizumab after high-dose cytarabine in relapsed\/refractory acute myeloid leukemia","volume":"2","author":"Zeidner","year":"2021","journal-title":"Blood Cancer Discov."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1182\/blood-2020-140521","article-title":"Updated results from a phase II study combining azacitidine and pembrolizumab in previously-untreated patients with higher-risk myelodysplastic syndrome","volume":"136","author":"Chien","year":"2020","journal-title":"Blood"},{"key":"ref_171","unstructured":"Daver, N.G., Basu, S., Garcia-Manero, G., Cortes, J.E., Ravandi, F., Jabbour, E., Hendrickson, S., Brandt, M., Pierce, S., and Gordon, T. (2017, January 9\u201312). Phase IB\/II study of nivolumab with azacytidine (AZA) in patients (pts) with relapsed AML. Proceedings of the 2017 ASH Annual Meeting, Atlanta, GA, USA."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1182\/blood-2021-146039","article-title":"Efficacy and safety of sabatolimab (MBG453) in combination with hypomethylating agents (HMAs) in patients (Pts) with very high\/high-risk myelodysplastic syndrome (vHR\/HR-MDS) and acute myeloid leukemia (AML): Final analysis from a phase Ib study","volume":"138","author":"Brunner","year":"2021","journal-title":"Blood"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1200\/JCO.22.01794","article-title":"Magrolimab in combination with azacitidine in patients with higher-risk myelodysplastic syndromes: Final results of a phase Ib study","volume":"41","author":"Sallman","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1182\/blood-2019-127345","article-title":"Multi-center phase 2 study of pembroluzimab (Pembro) and azacitidine (AZA) in patients with relapsed\/refractory acute myeloid leukemia (AML) and in newly diagnosed (\u2265 65 years) AML patients","volume":"134","author":"Gojo","year":"2019","journal-title":"Blood"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/s40164-023-00456-5","article-title":"Immune checkpoint inhibitors for multiple myeloma immunotherapy","volume":"12","author":"Liu","year":"2023","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/cei.13594","article-title":"Bone marrow-derived mesenchymal stem cells inhibit CD8+ T cell immune responses via PD-1\/PD-L1 pathway in multiple myeloma","volume":"205","author":"Liu","year":"2021","journal-title":"Clin. Exp. Immunol."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Huang, S., Zhao, Y., Liao, P., Wang, J., Li, Z., Tan, J., Zha, X., Chen, S., Li, Y., and Zhong, L. (2022). Different expression patterns of VISTA concurrent with PD-1, Tim-3, and TIGIT on T cell subsets in peripheral blood and bone marrow from patients with multiple myeloma. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1014904"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"e1261779","DOI":"10.1080\/2162402X.2016.1261779","article-title":"Adaptive resistance to anti-PD1 therapy by Tim-3 upregulation is mediated by the PI3K-Akt pathway in head and neck cancer","volume":"6","author":"Shayan","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s12253-011-9431-6","article-title":"Variations in suppressor molecule ctla-4 gene are related to susceptibility to multiple myeloma in a polish population","volume":"18","author":"Karabon","year":"2012","journal-title":"Pathol. Oncol. Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1046\/j.1365-2141.2001.02552.x","article-title":"Cytotoxic T-lymphocyte antigen-4 microsatellite polymorphism is associated with multiple myeloma","volume":"112","author":"Zheng","year":"2001","journal-title":"Br. J. Haematol."},{"key":"ref_181","first-page":"296","article-title":"Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-\u03b3 and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway","volume":"110","author":"Liu","year":"2007","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1182\/blood.V118.21.1829.1829","article-title":"Overexpression of CTLA-4 in the bone marrow of patients with multiple myeloma as a sign of local accumulation of immunosuppressive tregs\u2013perspectives for novel treatment strategies","volume":"118","author":"Braga","year":"2011","journal-title":"Blood"},{"key":"ref_183","first-page":"2475","article-title":"Prospective analysis of antigen-specific immunity, stem-cell antigens, and immune checkpoints in monoclonal gammopathy","volume":"126","author":"Dhodapkar","year":"2015","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"e448","DOI":"10.1016\/S2352-3026(19)30109-7","article-title":"Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): A randomised, open-label, phase 3 trial","volume":"6","author":"Usmani","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.1111\/bjh.15888","article-title":"Phase 1b trial of pembrolizumab monotherapy for relapsed\/refractory multiple myeloma: KEYNOTE-013","volume":"186","author":"Ribrag","year":"2019","journal-title":"Br. J. Haematol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"CT262","DOI":"10.1158\/1538-7445.AM2023-CT262","article-title":"Abstract CT262: Durable responses following anti-TIGIT (BMS-986207) and anti-LAG3 (BMS-980616) in combination with pomalidomide in relapsed myeloma: MMRF MyCheckpoint trial","volume":"83","author":"Cho","year":"2023","journal-title":"Cancer Res."},{"key":"ref_187","first-page":"2731","article-title":"Cancer immunoediting and immune dysregulation in multiple myeloma","volume":"136","author":"Nakamura","year":"2020","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41423-019-0344-8","article-title":"Exhaustion and senescence: Two crucial dysfunctional states of T cells in the tumor microenvironment","volume":"17","author":"Zhao","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"e127807","DOI":"10.1172\/jci.insight.127807","article-title":"Early alterations in stem-like\/marrow-resident T cells and innate and myeloid cells in preneoplastic gammopathy","volume":"4","author":"Bailur","year":"2019","journal-title":"JCI Insight"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1158\/2326-6066.CIR-15-0055","article-title":"T-cell exhaustion in multiple myeloma relapse after autotransplant: Optimal timing of immunotherapy","volume":"4","author":"Chung","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.ccell.2018.02.007","article-title":"Dysregulated IL-18 is a key driver of immunosuppression and a possible therapeutic target in the multiple myeloma microenvironment","volume":"33","author":"Nakamura","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s41375-021-01301-6","article-title":"Targeting LAG3\/GAL-3 to overcome immunosuppression and enhance anti-tumor immune responses in multiple myeloma","volume":"36","author":"Bae","year":"2022","journal-title":"Leukemia"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"eaar3593","DOI":"10.1126\/science.aar3593","article-title":"Pan-tumor genomic biomarkers for PD-1 checkpoint blockade\u2013based immunotherapy","volume":"362","author":"Cristescu","year":"2018","journal-title":"Science"},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Galanina, N., Bejar, R., Choi, M., Goodman, A., Wieduwilt, M., Mulroney, C., Kim, L., Yeerna, H., Tamayo, P., and Vergilio, J.-A. (2018). Comprehensive genomic profiling reveals diverse but actionable molecular portfolios across hematologic malignancies: Implications for next generation clinical trials. Cancers, 11.","DOI":"10.3390\/cancers11010011"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1158\/2159-8290.CD-16-0828","article-title":"Evolution of neoantigen landscape during immune checkpoint blockade in non\u2013small cell lung cancer","volume":"7","author":"Anagnostou","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1158\/1078-0432.CCR-16-1946","article-title":"Genomic profiling of patient-derived xenografts for lung cancer identifies B2M inactivation impairing immunorecognition","volume":"23","author":"Pereira","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1056\/NEJMoa1604958","article-title":"Mutations associated with acquired resistance to PD-1 blockade in melanoma","volume":"375","author":"Zaretsky","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.semcancer.2022.02.019","article-title":"Resistance to immune checkpoint blockade: Mechanisms, counter-acting approaches, and future directions","volume":"86","author":"Haddad","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/j.cell.2016.11.022","article-title":"Tumor interferon signaling regulates a multigenic resistance program to immune checkpoint blockade","volume":"167","author":"Benci","year":"2016","journal-title":"Cell"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.molcel.2021.01.010","article-title":"Interferon-\u03b3 induces tumor resistance to anti-PD-1 immunotherapy by promoting YAP phase separation","volume":"81","author":"Yu","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1158\/2159-8290.CD-16-1223","article-title":"Primary resistance to PD-1 blockade mediated by JAK1\/2 mutations","volume":"7","author":"Shin","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1093\/jnci\/88.2.100","article-title":"Loss of functional beta2-microglobulin in metastatic melanomas from five patients receiving immunotherapy","volume":"88","author":"Restifo","year":"1996","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nature15520","article-title":"Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy","volume":"527","author":"Peng","year":"2015","journal-title":"Nature"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.ccell.2019.08.008","article-title":"An evolutionarily conserved function of polycomb silences the MHC class I antigen presentation pathway and enables immune evasion in cancer","volume":"36","author":"Burr","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"5999","DOI":"10.1073\/pnas.1602069113","article-title":"NLRC5\/MHC class I transactivator is a target for immune evasion in cancer","volume":"113","author":"Yoshihama","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1038\/s41556-020-0562-4","article-title":"Acetylation-dependent regulation of PD-L1 nuclear translocation dictates the efficacy of anti-PD-1 immunotherapy","volume":"22","author":"Gao","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12943-024-02212-7","article-title":"Resistance mechanisms to immune checkpoint inhibitors: Updated insights","volume":"24","author":"Alsaafeen","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"E4041","DOI":"10.1073\/pnas.1720948115","article-title":"Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti\u2013PD-1 treatment","volume":"115","author":"Peranzoni","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"eaal3604","DOI":"10.1126\/scitranslmed.aal3604","article-title":"In vivo imaging reveals a tumor-associated macrophage\u2013mediated resistance pathway in anti\u2013PD-1 therapy","volume":"9","author":"Arlauckas","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"e1249561","DOI":"10.1080\/2162402X.2016.1249561","article-title":"Compensatory upregulation of PD-1, LAG-3, and CTLA-4 limits the efficacy of single-agent checkpoint blockade in metastatic ovarian cancer","volume":"6","author":"Huang","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"e121157","DOI":"10.1172\/jci.insight.121157","article-title":"CD226 opposes TIGIT to disrupt Tregs in melanoma","volume":"3","author":"Fourcade","year":"2018","journal-title":"JCI Insight"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1172\/JCI80445","article-title":"TIGIT and PD-1 impair tumor antigen\u2013specific CD8+ T cells in melanoma patients","volume":"125","author":"Chauvin","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_213","doi-asserted-by":"crossref","unstructured":"Almawash, S. (2025). Revolutionary Cancer Therapy for Personalization and Improved Efficacy: Strategies to Overcome Resistance to Immune Checkpoint Inhibitor Therapy. Cancers, 17.","DOI":"10.3390\/cancers17050880"},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Alsaafeen, B.H., Ali, B.R., and Elkord, E. (2025). Combinational therapeutic strategies to overcome resistance to immune checkpoint inhibitors. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1546717"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"101794","DOI":"10.1016\/j.tranon.2023.101794","article-title":"Charting new frontiers: Co-inhibitory immune checkpoint proteins in therapeutics, biomarkers, and drug delivery systems in cancer care","volume":"38","author":"Xiao","year":"2023","journal-title":"Transl. Oncol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1007\/s10555-021-09976-0","article-title":"Inhibitors of immune checkpoints\u2014PD-1, PD-L1, CTLA-4\u2014New opportunities for cancer patients and a new challenge for internists and general practitioners","volume":"40","author":"Wojtukiewicz","year":"2021","journal-title":"Cancer Metastasis Rev."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s10555-023-10139-6","article-title":"Next-generation immune checkpoint inhibitors as promising functional molecules in cancer therapeutics","volume":"42","author":"Dhasmana","year":"2023","journal-title":"Cancer Metastasis Rev."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.4110\/in.2022.22.e2","article-title":"Immune checkpoint inhibitors in 10 years: Contribution of basic research and clinical application in cancer immunotherapy","volume":"22","author":"Lee","year":"2022","journal-title":"Immune Netw."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41467-017-02630-w","article-title":"DNA methyltransferase inhibition upregulates MHC-I to potentiate cytotoxic T lymphocyte responses in breast cancer","volume":"9","author":"Luo","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"7017","DOI":"10.4049\/jimmunol.165.12.7017","article-title":"Activation of MHC class I, II, and CD40 gene expression by histone deacetylase inhibitors","volume":"165","author":"Magner","year":"2000","journal-title":"J. Immunol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1189\/jlb.0711339","article-title":"Histone deacetylase inhibitors impair NK cell viability and effector functions through inhibition of activation and receptor expression","volume":"91","author":"Rossi","year":"2012","journal-title":"J. Leukoc. Biol."},{"key":"ref_222","first-page":"600","article-title":"Epigenetic suppression of the antitumor cytotoxicity of NK cells by histone deacetylase inhibitor valproic acid","volume":"6","author":"Shi","year":"2016","journal-title":"Am. J. Cancer Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/14\/2292\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:07:35Z","timestamp":1760033255000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/14\/2292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,10]]},"references-count":222,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["cancers17142292"],"URL":"https:\/\/doi.org\/10.3390\/cancers17142292","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,10]]}}}