{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:05:00Z","timestamp":1789452300209,"version":"build-2803163510"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470688, 32000468"],"award-info":[{"award-number":["32470688, 32000468"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin Municipality","doi-asserted-by":"publisher","award":["24JCZDJC01400"],"award-info":[{"award-number":["24JCZDJC01400"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>MAIT and iNKT cells are unconventional T cell lineages that bridge innate and adaptive immunity and have been implicated in antitumor immune responses and immunotherapy outcomes. However, evidence to date has largely derived from individual studies of selected cancer types or specialized immune profiling cohorts. Whether MAIT and iNKT abundance provides reproducible clinical information across large, multi-cancer immune checkpoint blockade (ICB) cohorts remains insufficiently evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We applied an AI-based TCR\u03b2 inference framework to estimate MAIT and iNKT relative abundance from bulk TCR\u03b2 repertoires in healthy controls, patients with cancer, and ICB-treated cohorts. The main dataset included 1,619 samples from 420 healthy controls and 595 patients across 13 cancer types; response analyses used a discovery cohort of 964 samples from 436 patients across 9 cancer types and an independent validation cohort of 361 samples from 81 patients across 5 cancer types.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TCR\u03b2-inferred estimates showed that both MAIT and iNKT abundance were reduced in pretreatment cancer PBMCs compared with healthy controls, supporting systemic perturbation of unconventional T cells in cancer. Abundance estimates were also tissue dependent, with MAIT showing lower inferred abundance in tumor biopsies than in PBMCs. In ICB cohorts, baseline MAIT and iNKT estimates in PBMCs or tumors were insufficient to distinguish responders from non-responders. Although on-treatment tumor iNKT estimates showed a modest enrichment in responders in the discovery cohort, this pattern had limited standalone predictive value and was not reproduced as a robust biomarker in validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discusson<\/jats:title>\n                    <jats:p>These findings indicate that MAIT\/iNKT abundance captures cancer-associated and tissue dependent immune variation but has limited value alone for predicting ICB response, highlighting the need to incorporate functional state, spatial localization, and broader immune context.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1917317","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:36:12Z","timestamp":1789450572000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Systematic evaluation of MAIT and iNKT abundance as checkpoint blockade biomarkers"],"prefix":"10.3389","volume":"17","author":[{"given":"Yueyi","family":"Li","sequence":"first","affiliation":[{"name":"Academy of Medical Engineering and Translational Medicine, Tianjin University","place":["Tianjin, China"]},{"name":"State Key Laboratory of Advanced Medical Materials and Devices","place":["Tianjin, China"]},{"name":"Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LinLin","family":"Chen","sequence":"additional","affiliation":[{"name":"Academy of Medical Engineering and Translational Medicine, Tianjin University","place":["Tianjin, China"]},{"name":"State Key Laboratory of Advanced Medical Materials and Devices","place":["Tianjin, China"]},{"name":"Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwen","family":"Shan","sequence":"additional","affiliation":[{"name":"Academy of Medical Engineering and Translational Medicine, Tianjin University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Academy of Medical Engineering and Translational Medicine, Tianjin 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