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In this study, we evaluated the immunomodulatory effects of telmisartan using a syngeneic MC38 colorectal cancer model in C57BL\/6 mice. Daily intragastric administration of telmisartan significantly suppressed tumor growth and reduced endpoint tumor weight compared with controls. To elucidate the underlying mechanisms, we performed single-cell RNA sequencing on tumor-infiltrating CD45+ immune cells and revealed a macrophage-dominated immune landscape comprising multiple transcriptionally distinct subclusters. Telmisartan broadly downregulated pro-tumoral and M2-associated macrophage programs, including decreased expression of genes such as Mrc1 and Spp1, while also suppressing cell proliferation-related pathways. In contrast to its overall suppressive impact on macrophages, telmisartan increased the proportion of cytotoxic CD8+ T cells, reduced regulatory T cell counts, and enhanced major histocompatibility complex class I antigen presentation, consistent with an immune-activating effect. These results indicate that telmisartan reshapes the colorectal tumor immune microenvironment by simultaneously attenuating tumor-promoting macrophage activity and augmenting cytotoxic T cell responses. Overall, this study provides a single-cell framework to understand how angiotensin receptor blockade reshapes tumor-infiltrating immune programs, highlighting the translational potential of repurposing telmisartan for novel cancer immunotherapy strategies.<\/jats:p>","DOI":"10.3390\/cells15080729","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T12:01:22Z","timestamp":1776686482000},"page":"729","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Single-Cell Transcriptomics Reveals Immune Modulation by Telmisartan in Colorectal Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5786-5122","authenticated-orcid":false,"given":"Jinxin","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China"},{"name":"Medical Research Center, Peking 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