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Recent studies have shown that the efficacy of ICIs depends on the localization of immune cells, particularly T cells, within the tumor microenvironment (TME). Although the circadian clock is known to regulate immune cell migration into tumors, its role in orchestrating spatially precise intratumoral localization remains unclear. Here, we found that the distribution of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells within the TME varied according to the time of day, accompanied by diurnal expression of C\u2010X\u2010C chemokine receptor type 4 (CXCR4). The amplitude of the\n                    <jats:italic>Cxcr4<\/jats:italic>\n                    expression rhythm was more pronounced in tumor\u2010infiltrated T cells than in those from the spleen and was associated with time\u2010dependent changes in their migration toward CXCL12\u2010expressing cancer\u2010associated fibroblasts (CAFs). Reanalysis of single\u2010cell RNA\u2010seq data from T cells of lung cancer patients also revealed that upregulation of CXCR4 expression in tumor\u2010infiltrated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells was linked to TGF\u2010\u03b2\u2010SMAD signaling. The TGF\u2010\u03b2\u2010SMAD signaling\u2010mediated transactivation of\n                    <jats:italic>Cxcr4<\/jats:italic>\n                    was time\u2010dependently repressed by SMAD7, resulting in diurnal CXCR4 expression. Consequently, administration of a CXCR4 inhibitor during the circadian phase of elevated CXCR4 expression in tumor\u2010infiltrated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells promotes their dispersion throughout tumor tissues, thereby enhancing the efficacy of ICIs. Our findings highlight an unrecognized mechanism underlying diurnal changes in the aggregation and dispersion of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells within tumors, offering a novel approach to enhance the anti\u2010tumor immune effects of ICIs.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70252","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T11:19:23Z","timestamp":1763551163000},"page":"1740-1754","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["C\u2010X\u2010C chemokine receptor\n                    <scp>CXCR4<\/scp>\n                    mediates diurnal changes in the aggregation and dispersion of\n                    <scp>CD8<\/scp>\n                    <sup>+<\/sup>\n                    T cells within the tumor 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