{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:48:14Z","timestamp":1792615694395,"version":"4.5.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"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>\n                      The therapeutic landscape for deficient mismatch repair (dMMR) colorectal cancer (CRC) has been fundamentally transformed by the introduction of immune checkpoint inhibitors (ICIs). Yet, a significant fraction of patients exhibits primary or acquired resistance, underscoring a critical unmet need to decode the heterogeneity of tumor-infiltrating CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Identifying the effector subsets that truly drive tumor control will be essential for refining patient stratification and optimizing therapeutic interventions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      By leveraging a multi-dimensional approach that combined single-cell RNA sequencing (scRNA-seq), multiplex immunohistochemistry (mIHC), extensive clinical data mining, and\n                      <jats:italic>in vivo<\/jats:italic>\n                      murine models, we comprehensively delineated the phenotypic profile, regulatory networks, and clinical relevance of intratumoral CX3CR1\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We uncovered a unique CX3CR1\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell subset exhibiting a Temra-like terminal effector phenotype characterized by potent cytotoxicity (GNLY, PRF1) and low exhaustion. Clinically, enrichment of this population emerged as a strong, independent predictor of improved overall survival in CRC. Mechanistically, effective anti-PD-1 therapy revitalizes anti-tumor immunity by specifically promoting the proliferation and maintaining the function of these CX3CR1\n                      <jats:sup>+<\/jats:sup>\n                      effector cells within the tumor. SCENIC analysis further revealed that this differentiation pathway is orchestrated by\n                      <jats:italic>ETS1<\/jats:italic>\n                      ,\n                      <jats:italic>PRDM1<\/jats:italic>\n                      and\n                      <jats:italic>STAT1<\/jats:italic>\n                      driven regulatory network, which is markedly induced following PD-1 inhibition to enhance metabolic fitness and cellular recruitment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study characterizes CX3CR1\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells as a key effector subset predicting prognosis and immunotherapy response in colorectal cancer. These insights not only support their use as a clinically meaningful biomarker but also highlight the regulatory network orchestrated by\n                      <jats:italic>ETS1<\/jats:italic>\n                      and\n                      <jats:italic>PRDM1<\/jats:italic>\n                      as a promising avenue for overcoming immune resistance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1770119","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:57:35Z","timestamp":1773817055000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["CX3CR1 identifies a potent effector CD8+ T cell subset associated with anti-PD-1 therapeutic efficacy in colorectal cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiajin","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Tumor Biological Treatment, The Third 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