{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:08:32Z","timestamp":1784268512837,"version":"3.55.0"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"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>\n                    V\u03b39V\u03b42 T cells are blood-circulating, innate-like lymphocytes that contribute to tumor immunosurveillance and constitute over 95% of V\u03b42\n                    <jats:sup>+<\/jats:sup>\n                    \u03b3\u03b4 T cells, but how they perform antitumor or protumor functions remains unclear. Here, we comprehensively characterized V\u03b42\n                    <jats:sup>+<\/jats:sup>\n                    \u03b3\u03b4 T cells in paired peripheral blood and tumor samples from patients with renal cell carcinoma using flow cytometry and single-cell transcriptomic analysis. We identified two major V\u03b42\n                    <jats:sup>+<\/jats:sup>\n                    \u03b3\u03b4 T cell subsets distinguished by expression of CD16, which were present at variable proportions in both circulation and tumors. Notably, the proportion of CD16\n                    <jats:sup>+<\/jats:sup>\n                    V\u03b42\n                    <jats:sup>+<\/jats:sup>\n                    \u03b3\u03b4 T cells in blood closely reflected those in matched tumor tissues. Functionally, CD16\n                    <jats:sup>+<\/jats:sup>\n                    V\u03b42\n                    <jats:sup>+<\/jats:sup>\n                    \u03b3\u03b4 T cells exhibited potent cytotoxic capacity, characterized by high granzyme B expression and enhanced degranulation upon activation. In contrast, CD16\n                    <jats:sup>\u2013<\/jats:sup>\n                    V\u03b42\n                    <jats:sup>+<\/jats:sup>\n                    \u03b3\u03b4 T cells displayed central and effector memory features, expressed higher levels of CCR5, CXCR3, and granzyme K, and showed superior migratory capacity but limited cytotoxic activity. Single-cell RNA sequencing of tumor-infiltrating V\u03b42\n                    <jats:sup>+<\/jats:sup>\n                    \u03b3\u03b4 T cells identified four transcriptional clusters, including\n                    <jats:italic>FCGR3A<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic and\n                    <jats:italic>GZMK<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    inflammatory clusters corresponding to CD16\n                    <jats:sup>+<\/jats:sup>\n                    and CD16\n                    <jats:sup>\u2013<\/jats:sup>\n                    subsets, respectively. A\n                    <jats:italic>TOX<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    cluster exhibited progenitor-like features, giving rise to two divergent effector states along a differentiation trajectory. Within tumors, both CD16\n                    <jats:sup>+<\/jats:sup>\n                    and CD16\n                    <jats:sup>-<\/jats:sup>\n                    \u03b3\u03b4 T cells were broadly distributed and CD16\n                    <jats:sup>+<\/jats:sup>\n                    \u03b3\u03b4 T cells were more preferentially co-localized with tumor cells than CD16\n                    <jats:sup>-<\/jats:sup>\n                    \u03b3\u03b4 T cells. Collectively, these findings demonstrate that blood and intratumoral V\u03b42\n                    <jats:sup>+<\/jats:sup>\n                    \u03b3\u03b4 T cells are functionally heterogeneous and segregate into cytotoxic and inflammatory effector programs.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1864165","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:43:55Z","timestamp":1784267035000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Divergent cytotoxic and inflammatory functions of intratumoral V\u03b42+ \u03b3\u03b4 T cells in renal cell carcinoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Won Joon","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Immunology, Graduate School of Basic Medical Science, Sungkyunkwan University School of Medicine","place":["Suwon, Republic of Korea"]},{"name":"Personalized Cancer Immunotherapy Research Center, Sungkyunkwan University Medical Research Center","place":["Suwon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeyoun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Basic Medical Science, Sungkyunkwan University School of Medicine","place":["Suwon, Republic of Korea"]},{"name":"Personalized Cancer Immunotherapy Research Center, Sungkyunkwan University Medical Research Center","place":["Suwon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilanka Kalanapriya","family":"Dahanayake","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Basic Medical Science, Sungkyunkwan University School of Medicine","place":["Suwon, Republic of Korea"]},{"name":"Personalized Cancer Immunotherapy Research Center, Sungkyunkwan University Medical Research Center","place":["Suwon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon Yong","family":"Yeom","sequence":"additional","affiliation":[{"name":"Personalized Cancer Immunotherapy Research Center, Sungkyunkwan University Medical Research Center","place":["Suwon, Republic of Korea"]},{"name":"Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heeju","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Basic Medical Science, Sungkyunkwan University School of Medicine","place":["Suwon, Republic of Korea"]},{"name":"Personalized Cancer Immunotherapy Research Center, Sungkyunkwan University Medical Research Center","place":["Suwon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong","family":"Il Seo","sequence":"additional","affiliation":[{"name":"Personalized Cancer Immunotherapy Research Center, Sungkyunkwan University Medical Research Center","place":["Suwon, Republic of Korea"]},{"name":"Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Basic Medical Science, Sungkyunkwan University School of Medicine","place":["Suwon, Republic of Korea"]},{"name":"Personalized Cancer Immunotherapy Research Center, Sungkyunkwan University Medical Research Center","place":["Suwon, Republic of 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