CD300e as a Driver of Immunosuppressive Tumor Microenvironment in Colorectal Cancer

Tumor-associated macrophages (TAMs) are the predominant immune population within the tumor microenvironment (TME), playing a key role in promoting tumor growth and establishing an immunosuppressive environment that facilitate immune evasion. Here we report that the immune receptor CD300e is highly expressed by TAM in colorectal (CRC) and drives their immunosuppressive and pro-tumorigenic, correlating with reduced expression of MHC-II molecules, essential for antigen presentation. In vitro, CD300e-deficient macrophages exhibit enhanced pro-inflammatory activity and phagocytic capacity, coupled with reduced efferocytosis, suggesting a critical role for CD300e in promoting tumor progression. The depletion of CD300e, in vivo, results in a reduced tumor burden and enhanced survival in CRC mouse models, accompanied by a more robust anti-tumor immune response characterized by increased infiltration of activated CD4+ and CD8+ T cells producing IFN-γ. Our study provides comprehensive insights into the roles of CD300e in myeloid cells in CRC, highlighting its potential as a therapeutic target for reprogramming TAMs to support anti-tumor immunity.