{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:53:18Z","timestamp":1790931198724,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273199"],"award-info":[{"award-number":["82273199"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20221417"],"award-info":[{"award-number":["BK20221417"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Regulatory T cells (Tregs) are key mediators of immunosuppression in ovarian cancer, yet strategies for selectively targeting tumor\u2010infiltrating Tregs remain limited. CD4\n +<\/jats:sup>\n CCR8\n +<\/jats:sup>\n Tregs have been proposed as a highly suppressive subset, but their functional relevance and therapeutic potential require further investigation. Here, we demonstrate that CCR8 is preferentially expressed on tumor\u2010infiltrating CD4\n +<\/jats:sup>\n Tregs in syngeneic ID8 and B16 tumor models, accounting for a significantly higher proportion compared with CD4\n +<\/jats:sup>\n conventional T cells and CD8\n +<\/jats:sup>\n T cells (\n p<\/jats:italic>\n \u2009<\u20090.001). Functionally, CD4\n +<\/jats:sup>\n CCR8\n +<\/jats:sup>\n Tregs exhibited enhanced suppressive activity, markedly inhibiting IFN\u2010\u03b3 production by CD8\n +<\/jats:sup>\n T cells (\n p<\/jats:italic>\n \u2009<\u20090.01). The antagonist AZ084 significantly impaired Treg differentiation and alleviated Treg\u2010mediated suppression in\u00a0vitro (\n p<\/jats:italic>\n \u2009<\u20090.01). In\u00a0vivo, AZ084 treatment effectively suppressed tumor growth in both ovarian cancer and melanoma models (\n p<\/jats:italic>\n \u2009<\u20090.01), accompanied by a reduction in tumor\u2010infiltrating CD4\n +<\/jats:sup>\n CCR8\n +<\/jats:sup>\n Tregs and an increase in CD8\n +<\/jats:sup>\n T cell infiltration and effector function (\n p<\/jats:italic>\n \u2009<\u20090.05). Importantly, AZ084 had minimal impact on splenic immune cell composition (\n p<\/jats:italic>\n \u2009>\u20090.05), suggesting limited systemic immunotoxicity. Collectively, our findings identify CCR8 as a selective marker and functional regulator of tumor\u2010infiltrating Tregs. Targeting CCR8 with AZ084 represents a promising strategy to enhance antitumor immunity while preserving peripheral immune homeostasis, providing a potential therapeutic approach for ovarian cancer.\n <\/jats:p>","DOI":"10.1111\/cas.70465","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T02:55:09Z","timestamp":1783911309000},"page":"2719-2732","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Selective Depletion of Tumor\u2010Infiltrating CD4\n +<\/sup>\n CCR8\n +<\/sup>\n Tregs by AZ084, a Novel CCR8 Antagonist"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0924-5143","authenticated-orcid":false,"given":"Yepeng","family":"Mao","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine The First Affiliated Hospital with Nanjing Medical University Nanjing China"},{"name":"Branch of National Clinical Research Center for 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