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High infiltration of the tumor microenvironment (TME) with CD8<jats:sup>+<\/jats:sup> cytotoxic T cells (CTLs) and low infiltration with regulatory T cells (Treg) predicts the patients\u2019 responses to immunotherapy and long-term outcomes. To identify the mechanisms regulating long-term stability of CTL infiltration, we analyzed the impact of CTL-produced cytokines on the TME by co-culturing patient-isolated ascites cells with activated T cells. Unexpectedly, we observed that activated CTLs selectively induce cytotoxic T cell-attracting chemokines but not chemokines that attract T regulatory cells in ovarian cancer TME and tumor-associated myeloid cells, resulting in recruitment of additional CTLs without Tregs. This selectivity resulted from the unique dependence of CCL22 induction on both canonical and alternative NF-\u03baB and the suppression of alternative NF-\u03baB signaling by T cell-released IFN\u03b3. Our data demonstrate that T cell-produced IFN\u03b3 suppresses alternative NF-\u03baB signaling in TME-associated myeloid cells, allowing for the induction of CTL-attracting chemokines with the concomitant suppression of Treg-attracting CCL22. These novel functions of IFN\u03b3 and activated T cells in regulating the balance between canonical and alternative NF-\u03baB signaling in myeloid cells provide new opportunities to enhance and stabilize the selective CTL influx in the TME.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1681777","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T05:28:21Z","timestamp":1759987701000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["IFN\u03b3-mediated suppression of alternative NF-\u03baB in tumor-resident myeloid cells promotes selective recruitment of cytotoxic but not regulatory T 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