{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:23:01Z","timestamp":1789042981288,"version":"build-2803163510"},"reference-count":224,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMW","doi-asserted-by":"publisher","award":["91715337"],"award-info":[{"award-number":["91715337"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cancers"],"abstract":"<jats:p>The next frontier towards a cure for B-cell non-Hodgkin lymphomas (B-NHL) is autologous cellular immunotherapy such as immune checkpoint blockade (ICB), bispecific antibodies (BsAbs) and chimeric antigen receptor (CAR) T-cells. While highly successful in various solid malignancies and in aggressive B-cell leukemia, this clinical success is often not matched in B-NHL. T-cell subset skewing, exhaustion, expansion of regulatory T-cell subsets, or other yet to be defined mechanisms may underlie the lack of efficacy of these treatment modalities. In this review, a systematic overview of results from clinical trials is given and is accompanied by reported data on T-cell dysfunction. From these results, we distill the underlying pathways that might be responsible for the observed differences in clinical responses towards autologous T-cell-based cellular immunotherapy modalities between diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). By integration of the clinical and biological findings, we postulate strategies that might enhance the efficacy of autologous-based cellular immunotherapy for the treatment of B-NHL.<\/jats:p>","DOI":"10.3390\/cancers12123837","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T04:12:01Z","timestamp":1608523921000},"page":"3837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Overcoming the Hurdles of Autologous T-Cell-Based Therapies in B-Cell Non-Hodgkin Lymphoma"],"prefix":"10.3390","volume":"12","author":[{"given":"Jaco A. C.","family":"van Bruggen","sequence":"first","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Cancer Center Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Infection &amp; Immunity Institute, 1105 AZ Amsterdam, The Netherlands"},{"name":"Lymphoma and Myeloma Center Amsterdam, LYMMCARE, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0858-2482","authenticated-orcid":false,"given":"Anne W. J.","family":"Martens","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Cancer Center Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Infection &amp; Immunity Institute, 1105 AZ Amsterdam, The Netherlands"},{"name":"Lymphoma and Myeloma Center Amsterdam, LYMMCARE, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne H.","family":"Tonino","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Cancer Center Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Infection &amp; Immunity Institute, 1105 AZ Amsterdam, The Netherlands"},{"name":"Lymphoma and Myeloma Center Amsterdam, LYMMCARE, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnon P.","family":"Kater","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Cancer Center Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Infection &amp; Immunity Institute, 1105 AZ Amsterdam, The Netherlands"},{"name":"Lymphoma and Myeloma Center Amsterdam, LYMMCARE, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/S0140-6736(16)32407-2","article-title":"Non-Hodgkin lymphoma","volume":"390","author":"Armitage","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1002\/ajh.25595","article-title":"Chronic lymphocytic leukemia: 2020 update on diagnosis, risk stratification and treatment","volume":"94","author":"Hallek","year":"2019","journal-title":"Am. 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