{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:19:26Z","timestamp":1787552366509,"version":"build-2736575974"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>S-ketamine, a widely used clinical analgesic drug and also employed as a therapeutic regimen in cancer pain management, but whether S-ketamine influence on effector immune cells when conquering tumor cells remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we established effector T cells (chimeric antigen receptor T cells (CAR- T cells) and TCR-engineered T cells (TCR-T cells)) and treated with different concentrations of S-ketamine and investigated its impact on antitumor efficacy of effective T cell\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings demonstrated that S-ketamine treatment induced apoptosis in CAR- T and TCR-T cells, with higher concentrations leading to significant cell death. Furthermore, during coculture with target cells, increasing S-ketamine concentrations progressively dampened the early and late activation, impaired the tumor-killing capacity of both CAR-T and TCR-T cells, accompanied by reduced secretion of effector cytokines\u2014 particularly a striking downregulation of TNF-\u03b1 production. Meanwhile, the expression of immune checkpoint receptors in T cells was upregulation under target cell stimulation and S- ketamine treatment. Consistent with in vitro findings, escalating S- ketamine concentrations dampened the tumor inhibition of TCR-T cells in a xenograft tumor model, and also diminished the tumor-infiltrating capability of TCR-T cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>our study reveals that S- ketamine suppresses the cytotoxic function and promotes exhaustive phenotype of effector T cells when conquering the target cells, and providing some new guides in clinical use of S-ketamine on cancer pain therapy<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1852040","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T05:30:33Z","timestamp":1787549433000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["S-ketamine dampens effector T-cell function, thereby 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