{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T22:03:21Z","timestamp":1791756201109,"version":"4.3.4"},"reference-count":34,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T00:00:00Z","timestamp":1682121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro (AIRC)","doi-asserted-by":"publisher","award":["21198"],"award-info":[{"award-number":["21198"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro (AIRC)","doi-asserted-by":"publisher","award":["20564"],"award-info":[{"award-number":["20564"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro (AIRC)","doi-asserted-by":"publisher","award":["21147"],"award-info":[{"award-number":["21147"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro (AIRC)","doi-asserted-by":"publisher","award":["22791"],"award-info":[{"award-number":["22791"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Associazione Italiana Ricerca sul Cancro (AIRC)","doi-asserted-by":"publisher","award":["CP2_10\/2018"],"award-info":[{"award-number":["CP2_10\/2018"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondazione M. 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To elucidate a possible host immune activation following CAR-T-cell infusion, we investigated the effects of tisagenlecleucel administration on the patients\u2019 immune populations in 25 patients with R\/R diffuse large B-cell lymphoma (DLBCL) and B-lineage acute lymphoblastic leukemia (B-ALL). Methods: The modulation of CAR-T cells over time, the numeric changes, as well as the cytokine production capability of different lymphocyte populations and circulating cytokine levels, were analyzed. Results: Our results confirmed the ability of tisagenlecleucel to control the disease, with an overall response observed in 84.6% of DLBCL and in 91.7% of B-ALL patients at 1-month post-infusion, and showed that most patients who subsequently relapsed could undergo further treatment. Interestingly, we could document a significant increase in CD3+, CD4+, CD8+, and NK cells over time, as well as a decrease in Treg cells, and an increased IFN\u03b3 and TNF\u03b1 production by T lymphocytes. Conclusions: Taken together, our results indicate that in patients with DLBCL and B-ALL, the administration of tisagenlecleucel is capable of inducing a marked and prolonged in vivo modulation\/reshaping of the host immune system, both in children and adults.<\/jats:p>","DOI":"10.3390\/cancers15092411","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T02:06:11Z","timestamp":1682301971000},"page":"2411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Long-Term Host Immune Modulation Following Tisagenlecleucel Administration in Patients with Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic Leukemia"],"prefix":"10.3390","volume":"15","author":[{"given":"Anna","family":"Guarini","sequence":"first","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Radice","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6338-3112","authenticated-orcid":false,"given":"Nadia","family":"Peragine","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5345-7448","authenticated-orcid":false,"given":"Chiara","family":"Buracchi","sequence":"additional","affiliation":[{"name":"Tettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Stefania","family":"De Propris","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Di Rocco","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1043-0103","authenticated-orcid":false,"given":"Arianna","family":"Di Rocco","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Chiaretti","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Moretti","sequence":"additional","affiliation":[{"name":"Tettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Martelli","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5879-0610","authenticated-orcid":false,"given":"Adriana","family":"Balduzzi","sequence":"additional","affiliation":[{"name":"Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy"},{"name":"School of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1006-5946","authenticated-orcid":false,"given":"Giuseppe","family":"Gaipa","sequence":"additional","affiliation":[{"name":"Tettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Biondi","sequence":"additional","affiliation":[{"name":"Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy"},{"name":"School of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Fo\u00e0","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, 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Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/S0140-6736(21)00933-8","article-title":"Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): A phase 1b\/2 open-label study","volume":"398","author":"Berdeja","year":"2021","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Stock, S., Schmitt, M., and Sellner, L. (2019). Optimizing Manufacturing Protocols of Chimeric Antigen Receptor T Cells for Improved Anticancer Immunotherapy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246223"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"121016","DOI":"10.1016\/j.lfs.2022.121016","article-title":"Recent advances in the production, reprogramming, and application of CAR-T cells for treating hematological malignancies","volume":"309","author":"Vandghanooni","year":"2022","journal-title":"Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"eabd4344","DOI":"10.1126\/sciimmunol.abd4344","article-title":"A cross-talk between CAR T cell subsets and the tumor microenvironment is essential for sustained cytotoxic activity","volume":"6","author":"Boulch","year":"2021","journal-title":"Sci. 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