{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T11:05:08Z","timestamp":1789297508014,"version":"build-2803163510"},"reference-count":44,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"unspecified","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Oncode Accalerator"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,2,1]]},"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:p>\n                    Adoptive transfer of unmodified \u03b3\u03b4 T cells has shown limited clinical benefit, prompting a shift toward chimeric antigen receptor (CAR) engineering to enhance activation, persistence, and tumor specificity. CAR technology positions \u03b3\u03b4 T cells as promising carriers due to their innate-like cytotoxicity and HLA-independent recognition. Evidence from \u03b1\u03b2 CAR T-cell trials indicates that \u03b3\u03b4 CAR T cells can persist for months to years post-infusion, suggesting their potential contribution to long-term immune surveillance against cancer. Among \u03b3\u03b4 subsets, V\u03b39V\u03b42 T cells dominate peripheral blood and have been preferentially used for CAR engineering. Recent advances, however, enable the expansion of V\u03b41 T cells, known for their tissue residency and resistance to exhaustion. In a key comparative study, Li\n                    <jats:italic>et al<\/jats:italic>\n                    benchmarked PSCA-targeted CARs in V\u03b41, V\u03b39V\u03b42, and \u03b1\u03b2 T cells, showing similar short-term tumor control but distinct transcriptional and phenotypic programs. These findings highlight the need for subset-specific optimization of \u03b3\u03b4 CAR-T therapies. Early studies in hematologic malignancies could provide a practical proof of concept, before tackling the additional challenges of solid tumors. Such focused development may be essential to advance the \u03b3\u03b4 CAR-T field amid tightening industry investment.\n                  <\/jats:p>","DOI":"10.1136\/jitc-2025-014199","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T16:10:23Z","timestamp":1771949423000},"page":"e014199","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Commentary on \u201cComparative efficacy and safety of PSCA CAR-engineered V\u03b41 \u03b3\u03b4 T cells for immunotherapy of pancreatic cancer\u201d"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct05388305","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06592092","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Dorine A","family":"de Bont","sequence":"first","affiliation":[{"name":"Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trudy","family":"Straetemans","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands"},{"name":"Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsolt","family":"Sebesty\u00e9n","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3914-7806","authenticated-orcid":false,"given":"Jurgen","family":"Kuball","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands"},{"name":"Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"2026022408101629000_14.2.e014199.1","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/s41568-025-00830-x","article-title":"Disrupting the balance between activating and inhibitory receptors of \u03b3\u03b4T cells for effective cancer immunotherapy","volume":"25","author":"Beringer","year":"2025","journal-title":"Nat Rev Cancer"},{"key":"2026022408101629000_14.2.e014199.2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-19-0513"},{"key":"2026022408101629000_14.2.e014199.3","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41586-021-04390-6","article-title":"Decade-long leukaemia remissions with persistence of CD4+ CAR T cells","volume":"602","author":"Melenhorst","year":"2022","journal-title":"Nature New Biol"},{"key":"2026022408101629000_14.2.e014199.4","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1038\/s41591-023-02415-3","article-title":"Transcriptional signatures associated with persisting CD19 CAR-T cells in children with leukemia","volume":"29","author":"Anderson","year":"2023","journal-title":"Nat Med"},{"key":"2026022408101629000_14.2.e014199.5","doi-asserted-by":"crossref","unstructured":"GJJ K , W S , AD M , et al . 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