{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:39:54Z","timestamp":1790375994469,"version":"4.1.0"},"reference-count":100,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T00:00:00Z","timestamp":1596067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tumor cells use immune-checkpoint pathways to evade the host immune system and suppress immune cell function. These cells express programmed cell-death protein 1 ligand 1 (PD-L1)\/PD-L2, which bind to the programmed cell-death protein 1 (PD-1) present on cytotoxic T cells, trigger inhibitory signaling, and reduce cytotoxicity and T-cell exhaustion. Immune-checkpoint blockade can inhibit this signal and may serve as an effective therapeutic strategy in patients with solid tumors. Several trials have been conducted on immune-checkpoint inhibitor therapy in patients with malignant lymphoma and their efficacy has been reported. For example, in Hodgkin lymphoma, immune-checkpoint blockade has resulted in response rates of 65% to 75%. However, in non-Hodgkin lymphoma, the response rate to immune-checkpoint blockade was lower. In this review, we evaluate the biology of immune-checkpoint inhibition and the current data on its efficacy in malignant lymphoma, and identify the cases in which the treatment was more effective.<\/jats:p>","DOI":"10.3390\/ijms21155456","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T04:15:31Z","timestamp":1596168931000},"page":"5456","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Immune-Checkpoint Blockade Therapy in Lymphoma"],"prefix":"10.3390","volume":"21","author":[{"given":"Ayumi","family":"Kuzume","sequence":"first","affiliation":[{"name":"Department of Hematology, National Cancer Center Hospital East, Kashiwa 277\u20138577, Japan"},{"name":"Department of Hematology, Kameda Medical Center, Kamogawa 296\u20138602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5725-7187","authenticated-orcid":false,"given":"SungGi","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Hematology, National Cancer Center Hospital East, Kashiwa 277\u20138577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"Department of Hematology, National Cancer Center Hospital East, Kashiwa 277\u20138577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Minami","sequence":"additional","affiliation":[{"name":"Department of Hematology, National Cancer Center Hospital East, Kashiwa 277\u20138577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1182\/blood-2012-10-385591","article-title":"The role of B7 family molecules in hematologic malignancy","volume":"121","author":"Greaves","year":"2013","journal-title":"Blood"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.3892\/ol.2016.4774","article-title":"TIM-3 expression in lymphoma cells predicts chemoresistance in patients with adult T-cell leukemia\/lymphoma","volume":"12","author":"Horlad","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.jtho.2016.10.022","article-title":"Establishment of a Conditional Transgenic Mouse Model Recapitulating EML4-ALK-Postive Human Non\u2013Small Cell Lung Cancer","volume":"12","author":"Pyo","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1182\/blood-2006-04-015164","article-title":"Expression of LAG-3 by tumor-infiltrating lymphocytes is coincident with the suppression of latent membrane antigen\u2013specific CD8+ T-cell function in Hodgkin lymphoma patients","volume":"108","author":"Gandhi","year":"2006","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"61425","DOI":"10.18632\/oncotarget.18251","article-title":"Expression of LAG-3 defines exhaustion of intratumoral PD-1+ T cells and correlates with poor outcome in follicular lymphoma","volume":"8","author":"Yang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.18632\/oncotarget.26771","article-title":"The immune checkpoint molecules PD-1, PD-L1, TIM-3 and LAG-3 in diffuse large B-cell lymphoma","volume":"10","author":"Chen","year":"2019","journal-title":"Oncotarget"},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1056\/NEJMoa1414428","article-title":"Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma","volume":"372","author":"Postow","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S1470-2045(15)70076-8","article-title":"Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): A randomised, controlled, open-label, phase 3 trial","volume":"16","author":"Weber","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1200\/JCO.2013.53.0105","article-title":"Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab","volume":"32","author":"Topalian","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1182\/blood-2003-07-2594","article-title":"Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma","volume":"103","author":"Marshall","year":"2004","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1158\/2326-6066.CIR-17-0325","article-title":"Complex Immune Evasion Strategies in Classical Hodgkin Lymphoma","volume":"5","author":"Wein","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1182\/blood-2017-03-770719","article-title":"Topological analysis reveals a PD-L1-associated microenvironmental niche for Reed-Sternberg cells in Hodgkin lymphoma","volume":"130","author":"Carey","year":"2017","journal-title":"Blood"},{"key":"ref_16","first-page":"5716","article-title":"Specific Recruitment of CC Chemokine Receptor 4\u2013Positive Regulatory T Cells in Hodgkin Lymphoma Fosters Immune Privilege","volume":"66","author":"Ishida","year":"2006","journal-title":"Cancer Res. Treat."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1182\/blood-2013-06-508044","article-title":"Defining characteristics of classical Hodgkin lymphoma microenvironment T-helper cells","volume":"122","author":"Greaves","year":"2013","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1182\/blood-2006-12-064360","article-title":"RNA fingerprints provide direct evidence for the inhibitory role of TGF\u03b2 and PD-1 on CD4+ T cells in Hodgkin lymphoma","volume":"110","author":"Chemnitz","year":"2007","journal-title":"Blood"},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.1182\/blood-2010-05-282780","article-title":"Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma","volume":"116","author":"Green","year":"2010","journal-title":"Blood"},{"key":"ref_21","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_22","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":"Younes","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3733","DOI":"10.1200\/JCO.2016.67.3467","article-title":"Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure","volume":"34","author":"Armand","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1200\/JCO.19.00315","article-title":"Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study","volume":"37","author":"Ramchandren","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1182\/blood-2017-10-811224","article-title":"Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma","volume":"131","author":"Herrera","year":"2018","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.canrad.2018.05.002","article-title":"Anti-PD-1 immunotherapy in combination with sequential involved-site radiotherapy in heavily pretreated refractory Hodgkin lymphoma","volume":"23","author":"Gilardin","year":"2019","journal-title":"Cancer\/Radioth\u00e9rapie"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1667\/RR15048.1","article-title":"Complete Local and Abscopal Responses from a Combination of Radiation and Nivolumab in Refractory Hodgkin\u2019s Lymphoma","volume":"190","author":"Qin","year":"2018","journal-title":"Radiat. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1182\/blood-2018-03-841262","article-title":"Prolonged remissions after anti-PD-1 discontinuation in patients with Hodgkin lymphoma","volume":"131","author":"Manson","year":"2018","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4232","DOI":"10.1158\/1078-0432.CCR-10-2660","article-title":"Timmerman Programmed Death Ligand 1 Is Expressed by Non\u2013Hodgkin Lymphomas and Inhibits the Activity of Tumor-Associated T Cells","volume":"17","author":"Andorsky","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.humpath.2016.03.005","article-title":"Evaluation of the diagnostic and prognostic value of PDL1 expression in Hodgkin and B-cell lymphomas","volume":"54","author":"Menter","year":"2016","journal-title":"Hum. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.biopha.2015.08.037","article-title":"Prognostic value of PD-1 and TIM-3 on CD3+ T cells from diffuse large B-cell lymphoma","volume":"75","author":"Zhang","year":"2015","journal-title":"Biomed. Pharmacother."},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"4199","DOI":"10.1200\/JCO.2012.48.3685","article-title":"Disabling Immune Tolerance by Programmed Death-1 Blockade With Pidilizumab After Autologous Hematopoietic Stem-Cell Transplantation for Diffuse Large B-Cell Lymphoma: Results of an International Phase II Trial","volume":"31","author":"Armand","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_36","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_37","doi-asserted-by":"crossref","first-page":"6446","DOI":"10.1158\/1078-0432.CCR-09-1339","article-title":"Phase I Study of Ipilimumab, an Anti-CTLA-4 Monoclonal Antibody, in Patients with Relapsed and Refractory B-Cell Non-Hodgkin Lymphoma","volume":"15","author":"Ansell","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1080\/10428194.2018.1452217","article-title":"An abscopal effect may augment PD-1 inhibition in refractory classical Hodgkin lymphoma","volume":"59","author":"Wight","year":"2018","journal-title":"Leuk. Lymphoma"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e445","DOI":"10.1016\/S2352-3026(15)00150-7","article-title":"Ratios of T-cell immune eff ectors and checkpoint molecules as prognostic biomarkers in diff use large B-cell lymphoma: A population-based study","volume":"2","author":"Keane","year":"2015","journal-title":"Lancet Haematol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1182\/blood-2015-10-673236","article-title":"Targetable genetic features of primary testicular and primary central nervous system lymphomas","volume":"127","author":"Chapuy","year":"2016","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1097\/PAS.0000000000000297","article-title":"Expression of Programmed Cell Death 1 Ligand 2 (PD-L2) Is a Distinguishing Feature of Primary Mediastinal (Thymic) Large B-cell Lymphoma and Associated With PDCD1LG2 Copy Gain","volume":"38","author":"Shi","year":"2014","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_42","first-page":"4","article-title":"Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma","volume":"123","author":"Twa","year":"2014","journal-title":"Brief Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1182\/blood-2015-11-683003","article-title":"Comprehensive characterization of programmed death ligand structural rearrangements in B-cell non-Hodgkin lymphomas","volume":"128","author":"Chong","year":"2016","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.3109\/10428194.2014.985673","article-title":"Structural genomic alterations in primary mediastinal large B-cell lymphoma","volume":"56","author":"Twa","year":"2015","journal-title":"Leuk. Lymphoma"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1097\/PAS.0000000000000473","article-title":"Identification of Primary Mediastinal Large B-cell Lymphoma at Nonmediastinal Sites by Gene Expression Profiling","volume":"39","author":"Yuan","year":"2015","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3291","DOI":"10.1200\/JCO.19.01389","article-title":"Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma","volume":"37","author":"Armand","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6358","DOI":"10.1200\/JCO.2005.26.856","article-title":"Molecular Pathogenesis of Follicular Lymphoma: A Cross Talk of Genetic and Immunologic Factors","volume":"23","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1158\/1078-0432.CCR-13-2367","article-title":"Pattern of CD14\u00fe Follicular Dendritic Cells and PD1\u00fe T Cells Independently Predicts Time to Transformation in Follicular Lymphoma","volume":"20","author":"Smeltzer","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1182\/blood-2012-04-421826","article-title":"High PD-1 expression and suppressed cytokine signaling distinguish T cells infiltrating follicular lymphoma tumors from peripheral T cells","volume":"121","author":"Myklebust","year":"2013","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1200\/JCO.2008.18.0513","article-title":"High Numbers of Tumor-Infiltrating Programmed Cell Death 1\u2013Positive Regulatory Lymphocytes Are Associated With Improved Overall Survival in Follicular Lymphoma","volume":"27","author":"Carreras","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.humpath.2010.08.015","article-title":"Follicular programmed death 1\u2013positive lymphocytes in the tumor microenvironment are an independent prognostic factor in follicular lymphoma","volume":"42","author":"Richendollar","year":"2011","journal-title":"Hum. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S1470-2045(13)70551-5","article-title":"Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: A single group, open-label, phase 2 trial","volume":"15","author":"Westin","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/nrc1452","article-title":"Epstein\u2013Barr Virus: 40 years on","volume":"4","author":"Young","year":"2004","journal-title":"Nat. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/leu.2008.272","article-title":"PD-1\/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia\/lymphoma patients","volume":"23","author":"Kozako","year":"2009","journal-title":"Leukemia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1158\/1078-0432.CCR-11-1942","article-title":"Constitutive AP-1 Activity and EBV Infection Induce PD-L1 in Hodgkin Lymphomas and Posttransplant Lymphoproliferative Disorders: Implications for Targeted Therapy","volume":"18","author":"Green","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3462","DOI":"10.1158\/1078-0432.CCR-13-0855","article-title":"PD-L1 Expression Is Characteristic of a Subset of Aggressive B-cell Lymphomas and Virus-Associated Malignancies","volume":"19","author":"Chen","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1182\/blood-2015-02-630632","article-title":"EBV-positive large B-cell lymphomas in young patients: A nodal lymphoma with evidence for a tolerogenic immune environment","volume":"126","author":"Nicolae","year":"2015","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1038\/s41375-019-0380-5","article-title":"Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas","volume":"33","author":"Kataoka","year":"2019","journal-title":"Leukemia"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1182\/blood-2013-03-489708","article-title":"EBV-positive diffuse large B-cell lymphoma of the elderly","volume":"122","author":"Ok","year":"2013","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/nrg.2016.13","article-title":"Epigenetic modulators, modifiers and mediators in cancer aetiology and progression","volume":"17","author":"Feinberg","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/ni.3630","article-title":"TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells","volume":"18","author":"Tsagaratou","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1182\/blood-2016-12-756841","article-title":"PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK\/T-cell lymphoma failing l-asparaginase","volume":"129","author":"Kwong","year":"2017","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13045-016-0341-7","article-title":"PD-L1 is upregulated by EBV-driven LMP1 through NF-\u03baB pathway and correlates with poor prognosis in natural killer\/T-cell lymphoma","volume":"9","author":"Bi","year":"2016","journal-title":"J. Hematol. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"611","DOI":"10.4143\/crt.2018.191","article-title":"Comparison of Efficacy of Pembrolizumab between Epstein-Barr Virus\u2013Positive and \u2013Negative Relapsed or Refractory Non-Hodgkin Lymphomas","volume":"51","author":"Kim","year":"2019","journal-title":"Cancer Res. Treat."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1182\/blood-2009-11-253039","article-title":"The role of tumor histogenesis, FDG-PET, and short-course EPOCH with dose-dense rituximab (SC-EPOCH-RR) in HIV-associated diffuse large B-cell lymphoma","volume":"115","author":"Dunleavy","year":"2010","journal-title":"Blood"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1038\/nm1482","article-title":"Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction","volume":"12","author":"Trautmann","year":"2006","journal-title":"Nat. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/nm.3109","article-title":"Inadequate T follicular cell help impairs B cell immunity during HIV infection","volume":"19","author":"Cubas","year":"2013","journal-title":"Nat. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1182\/blood-2011-08-373738","article-title":"How I treat HIV-associated lymphoma","volume":"119","author":"Dunleavy","year":"2012","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1097\/CJI.0000000000000240","article-title":"Nivolumab Treatment for Cancers in the HIV-infected Population","volume":"41","author":"Chang","year":"2018","journal-title":"J. Immunother."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1182\/blood-2016-09-738385","article-title":"Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed\/refractory lymphoma","volume":"129","author":"Merryman","year":"2017","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.4049\/jimmunol.171.3.1272","article-title":"Blockade of Programmed Death-1 Engagement Accelerates Graft-Versus-Host Disease Lethality by an IFN-\u03b3-Dependent Mechanism","volume":"171","author":"Blazar","year":"2003","journal-title":"J. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6368","DOI":"10.4049\/jimmunol.162.11.6368","article-title":"Opposing Roles of CD28:B7 and CTLA-4:B7 Pathways in Regulating In Vivo Alloresponses in Murine Recipients of MHC Disparate T Cells","volume":"162","author":"Blazar","year":"1999","journal-title":"J. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3062","DOI":"10.1182\/blood-2013-05-500801","article-title":"Host programmed death ligand 1 is dominant over programmed death ligand 2 expression in regulating graft-versus-host disease lethality","volume":"122","author":"Saha","year":"2013","journal-title":"Blood"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"560","DOI":"10.4049\/jimmunol.1402157","article-title":"B7H1\/CD80 Interaction Augments PD-1\u2013Dependent T Cell Apoptosis and Ameliorates Graft-versus-Host Disease","volume":"194","author":"Deng","year":"2015","journal-title":"J. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1182\/blood-2008-07-168468","article-title":"CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation","volume":"113","author":"Bashey","year":"2009","journal-title":"Blood"},{"key":"ref_76","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_77","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1182\/blood-2016-11-749556","article-title":"Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin lymphoma","volume":"129","author":"Herbaux","year":"2017","journal-title":"Blood"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1182\/blood-2017-01-761346","article-title":"PD-1 blockade for relapsed lymphoma post\u2013allogeneic hematopoietic cell transplant: High response rate but frequent GVHD","volume":"130","author":"Haverkos","year":"2017","journal-title":"Blood"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/0092-8674(91)90314-O","article-title":"The cytoplasmic domain of the T cell receptor \u03b6 chain is sufficient to couple to receptor-associated signal transduction pathways","volume":"64","author":"Irving","year":"1991","journal-title":"Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e20","DOI":"10.1200\/JCO.2006.05.9964","article-title":"Treatment of Metastatic Renal Cell Carcinoma With Autologous T-Lymphocytes Genetically Retargeted Against Carbonic Anhydrase IX: First Clinical Experience","volume":"24","author":"Lamers","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/sj.mt.6300104","article-title":"Adoptive Transfer of Chimeric Antigen Receptor Re-directed Cytolytic T Lymphocyte Clones in Patients with Neuroblastoma","volume":"15","author":"Park","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6106","DOI":"10.1158\/1078-0432.CCR-06-1183","article-title":"A Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer","volume":"12","author":"Kershaw","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1182\/blood-2010-04-281931","article-title":"Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19","volume":"116","author":"Kochenderfer","year":"2010","journal-title":"Blood"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1056\/NEJMoa1103849","article-title":"Chimeric Antigen Receptor\u2013Modified T Cells in Chronic Lymphoid Leukemi","volume":"365","author":"Porter","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"95ra73","DOI":"10.1126\/scitranslmed.3002842","article-title":"T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia","volume":"3","author":"Kalos","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1056\/NEJMoa1407222","article-title":"Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia","volume":"371","author":"Maude","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1056\/NEJMoa1709866","article-title":"Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia","volume":"378","author":"Maude","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1056\/NEJMoa1708566","article-title":"Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas","volume":"377","author":"Schuster","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma","volume":"377","author":"Neelapu","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1038\/mt.2013.154","article-title":"Persistence and Efficacy of Second Generation CAR T Cell Against the LeY Antigen in Acute Myeloid Leukemia","volume":"21","author":"Ritchie","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/mt.2014.164","article-title":"Treatment of CD33-directed Chimeric Antigen Receptor-modified T Cells in One Patient With Relapsed and Refractory Acute Myeloid Leukemia","volume":"23","author":"Wang","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e54","DOI":"10.1016\/j.clml.2019.09.083","article-title":"CT053, Anti-BCMA CAR T-cell therapy for Relapsed\/Refractory Multiple Myeloma: Proof of Concept results from a Phase I Study","volume":"19","author":"Hao","year":"2019","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/imr.12393","article-title":"Harnessing T cells to fight cancer with BiTE_ antibody constructs\u2013past developments and future directions","volume":"270","author":"Klinger","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"6389","DOI":"10.4049\/jimmunol.1103019","article-title":"Chimeric Antigen Receptor T Cells Shape Myeloid Cell Function within the Tumor Microenvironment through IFN-\u03b3 and GM-CSF","volume":"188","author":"Spear","year":"2012","journal-title":"J. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1200\/JCO.2010.32.7270","article-title":"Targeted Therapy with the T-Cell\u2013Engaging Antibody Blinatumomab of Chemotherapy-Refractory Minimal Residual Disease in B-Lineage Acute Lymphoblastic Leukemia Patients Results in High Response Rate and Prolonged Leukemia-Free Survival","volume":"29","author":"Topp","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s40164-017-0074-5","article-title":"Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed\/refractory ALL","volume":"6","author":"Kratzer","year":"2017","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1200\/JCO.2016.69.3531","article-title":"Complete Hematologic and Molecular Response in Adult Patients With Relapsed\/Refractory Philadelphia Chromosome\u2013Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study","volume":"35","author":"Martinelli","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1056\/NEJMoa1609783","article-title":"Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia","volume":"376","author":"Kantarjian","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1200\/JCO.2014.59.1586","article-title":"Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed\/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study","volume":"34","author":"Goebeler","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1182\/blood-2015-06-651380","article-title":"Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed\/refractory diffuse large B-cell lymphoma","volume":"127","author":"Viardot","year":"2016","journal-title":"Blood"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/15\/5456\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:53:05Z","timestamp":1760176385000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/15\/5456"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,30]]},"references-count":100,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["ijms21155456"],"URL":"https:\/\/doi.org\/10.3390\/ijms21155456","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,30]]}}}