{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:43:13Z","timestamp":1792183393312,"version":"4.4.0"},"reference-count":16,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"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>T-cell\/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare, aggressive subtype of diffuse large B-cell lymphoma characterized by a profoundly immunosuppressive tumor microenvironment. PD-L1 overexpression by tumor cells is a recognized immune escape mechanism and may underlie resistance to cellular therapies, including CAR T-cell therapy. We report a case of a 29-year-old woman with refractory stage IV-B THRLBCL treated with anti-CD19 CAR T-cell therapy (varnimcabtagene autoleucel), who achieved an initial response (day +28) but experienced disease progression by day +100 despite robust CAR T-cell expansion. Peripheral blood analysis revealed persistent absolute B-cell aplasia, while bone marrow biopsy confirmed CD19-positive disease. Comparative immunohistochemistry demonstrated markedly increased PD-L1 expression in post-CAR T-cell samples, suggesting adaptive immune resistance via PD-1\/PD-L1-mediated CAR T-cell inhibition. Nivolumab was initiated at month +4 to overcome this checkpoint-mediated resistance. Notably, a complete metabolic response was documented on PET\/CT after four doses of nivolumab (month +6). The patient remains in sustained remission, with persistent B-cell aplasia, four years post-intervention. This case provides clinical and pathological evidence supporting the use of immune checkpoint blockade to rescue CAR T-cell efficacy, highlighting the potential of this synergistic approach in THRLBCL and possibly other B-cell malignancies exhibiting similar immune evasion.<\/jats:p>","DOI":"10.3390\/ijms26199265","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:09:42Z","timestamp":1758614982000},"page":"9265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Combining CAR T-Cell Therapy and Nivolumab to Overcome Immune Resistance in THRLBCL: A Case Report"],"prefix":"10.3390","volume":"26","author":[{"given":"Daniel","family":"Munarriz","sequence":"first","affiliation":[{"name":"Department of Hematology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriana","family":"L\u00f3pez-Godino","sequence":"additional","affiliation":[{"name":"Department of Hematology, Centro Regional de Hemodonaci\u00f3n, IMIB-Pascual Parrilla, Hospital Universitario Morales-Meseguer, 30008 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8688-1202","authenticated-orcid":false,"given":"Nuria","family":"Martinez-Cibrian","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Faculty of Medicine, University of Barcelona, 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2942-1362","authenticated-orcid":false,"given":"Nil","family":"Albiol","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Faculty of Medicine, University of Barcelona, 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Brillembourg","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Navarro-Vel\u00e1zquez","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Barcelona, 08007 Barcelona, Spain"},{"name":"Department of Immunology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Espa\u00f1ol-Rego","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 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Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Alserawan","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2346-5324","authenticated-orcid":false,"given":"Daniel","family":"Benitez-Ribas","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Magnano","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Gonzalo","family":"Correa","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4233-5031","authenticated-orcid":false,"given":"Andrea","family":"Rivero","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Faculty of Medicine, University of Barcelona, 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9528-4971","authenticated-orcid":false,"given":"Pablo","family":"Mozas","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Cl\u00ednic, 08036 Barcelona, 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Frutos","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Hospital C.U. Virgen de la Arrixaca, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Balagu\u00e9-Ponz","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Department of Pathology, Hospital Cl\u00ednic de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Urbano-Ispizua","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Faculty of Medicine, University of Barcelona, 08007 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Josep Carreras Research Institute, 08916 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3310-5557","authenticated-orcid":false,"given":"Europa Azucena","family":"Gonz\u00e1lez-Navarro","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3064-1648","authenticated-orcid":false,"given":"Manel","family":"Juan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Barcelona, 08007 Barcelona, Spain"},{"name":"Department of Immunology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Cl\u00ednic-Sant Joan de D\u00e9u Immunotherapy Platform, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Delgado","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Faculty of Medicine, University of Barcelona, 08007 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4699-6862","authenticated-orcid":false,"given":"Valent\u00edn","family":"Ortiz-Maldonado","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Faculty of Medicine, University of Barcelona, 08007 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1182\/blood.2020006464","article-title":"Spatial signatures identify immune escape via PD-1 as a defining feature of T-cell\/histiocyte-rich large B-cell lymphoma","volume":"137","author":"Griffin","year":"2021","journal-title":"Blood"},{"key":"ref_2","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. 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