{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T19:16:11Z","timestamp":1793214971859,"version":"4.5.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"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":"\n Introduction<\/jats:title>\n \n Recent findings reveal that the precursors of exhausted CD8\n +<\/jats:sup>\n T (CD8\n +<\/jats:sup>\n Tpex) cells possess stem-like signatures in tumor immunity, which originate from tumor draining lymph node (TdLN)-derived tumor-specific memory (CD8\n +<\/jats:sup>\n T\n TSM<\/jats:sub>\n ) cells. Both of these T subsets can be collectively referred to as stem-like CD8\n +<\/jats:sup>\n T cells, which demonstrate robust self-renewal ability and can proliferate and differentiate into transitory effector-like exhausted T cells (Tex\n int<\/jats:sup>\n ). There are reports that chemotherapeutic drugs can promote the antitumor immune responses of patients by increasing the number of CD8\n +<\/jats:sup>\n T cells; however, whether chemotherapeutic drugs increase these two stem-like CD8\n +<\/jats:sup>\n T cells remain further exploration.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Tpex cell-associated subpopulations in human colorectal tumors were analyzed by using single-cell sequencing data. CT26 and B16 tumor models of wild type and Eomes conditional knockout mice were constructed, and the changes of T\n TSM<\/jats:sub>\n , Tpex and Tex subsets in mice were dissected by flow cytometry after treatment with decitabine (DAC), doxorubicin (DOX) and 5-Fluorouracil (5-FU).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In this study, we demonstrated that DAC and 5-FU expanded CD8\n +<\/jats:sup>\n T\n TSM<\/jats:sub>\n cells in TdLNs. At the same time, we validated that DAC and 5-FU substantially promoted the expansion of CD62L\n +<\/jats:sup>\n CD8\n +<\/jats:sup>\n Tpex cells and subsequently increased effector function of CX3CR1\n +<\/jats:sup>\n CD8\n +<\/jats:sup>\n Tex\n int<\/jats:sup>\n cells. In addition, the conditional knockout of transcription factor Eomes in CD8\n +<\/jats:sup>\n T cells partially eliminated DAC-amplified CD62L\n +<\/jats:sup>\n CD8\n +<\/jats:sup>\n Tpex cells, but had no effect on such CD8\n +<\/jats:sup>\n T subset expanded by 5-FU.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The present study demonstrated that both DAC and 5-FU promoted the differentiation of stem-like CD8\n +<\/jats:sup>\n T\n TSM<\/jats:sub>\n cells in TdLNs and significantly enhanced the differentiation and expansion of stem-like CD62L\n +<\/jats:sup>\n CD8\n +<\/jats:sup>\n Tpex and CX3CR1\n +<\/jats:sup>\n Tex\n int<\/jats:sup>\n cells in tumor microenvironment. The knockout of Eomes partially influenced the role of DAC in promoting the differentiation and expansion of stem-like CD8\n +<\/jats:sup>\n T cells.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1533857","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T01:43:20Z","timestamp":1743471800000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Two chemotherapeutic agents expand stem-like CD62L+CD8+ T cells in antitumor immune 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