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CD300e as a driver of immunosuppressive tumor microenvironment and colorectal cancer progression via macrophages reprogramming [scRNA-Seq]

ABSTRACT: Colorectal cancer progression is strongly influenced by the tumor microenvironment, particularly by tumor-associated macrophages, which often acquire immunosuppressive features that dampen antitumor immunity. CD300e is a myeloid receptor known to modulate immune responses, but its role in CRC remains unexplored. Here, we show that CD300e is selectively upregulated in tumor-infiltrating monocytes and monocyte-derived macrophages in human CRC, displaying an immunosuppressive phenotype characterized by reduced antigen presentation. Using in vitro co-cultures of patient-derived tumor organoids and human monocytes, we demonstrate that tumor-derived signals are sufficient to induce CD300e expression and skew macrophages toward a pro-tumorigenic profile. To investigate the functional relevance of CD300e, we employed CD300e knockout mice in AOM/DSS-induced and MC38 subcutaneous CRC models. In both settings, CD300e deletion led to reduced tumor burden, enhanced major histocompatibility complex expression in TAMs, and improved T cell-mediated antitumor responses. Transcriptomic and functional analyses revealed that CD300e-deficient macrophages display increased phagocytic activity, upregulated antigen presentation pathways, and a greater ability to support T cell proliferation and cytotoxicity. Adoptive transfer experiments confirmed that CD300e expression on macrophages alone is sufficient to promote tumor growth and suppress effector T cell function. These findings identify CD300e as a key regulator of macrophage-mediated immune suppression in CRC and suggest that targeting CD300e may represent a novel strategy to reprogram TAMs and enhance the efficacy of cancer immunotherapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE301367 | GEO | 2025/12/30

REPOSITORIES: GEO

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CD300e as a driver of immunosuppressive tumor microenvironment and colorectal cancer progression via macrophages reprogramming [scRNA-Seq]

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