{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:06:41Z","timestamp":1789538801377,"version":"build-2803163510"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Chimeric antigen receptor (CAR) T cells are capable to eliminate cancer cells in the treatment of hematologic malignancies, yet the efficacy is frequently inconsistent and limited by cancer cell resistance and antigen-loss resulting in early tumor relapses. While CAR T cells are deemed to be the primary effectors in controlling the tumor, maturing evidence indicates that therapeutic outcomes are shaped by a broader immune cell network involving both the endogenous adaptive and innate immunity. In this review, we reframe CAR T cell therapy as the induction of a multi-system immune response rather than a uni-directional cytotoxic cell-autonomous intervention. We discuss the respective contributions of CAR T cells, innate immune cells, and host adaptive immunity in controlling tumor progression and outline strategies to recruit innate immunity using TRUCKs, armored CAR T cells, as well as immunological adjuvants to surmount current limitations. Finally, we address the risks associated with excessive innate immune activation and propose that a calibrated, broad immune cell activation should be viewed as design principle for next-generation CAR T cell therapies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1955025","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:31:26Z","timestamp":1789536686000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CAR T cell cancer immunotherapy: who does the job?"],"prefix":"10.3389","volume":"17","author":[{"given":"Dennis Christoph","family":"Harrer","sequence":"first","affiliation":[{"name":"Leibniz Institute for Immunotherapy, Div. 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