CD300e deficiency drives the immunostimulatory profile of tumor-infiltrating macrophages in a colorectal cancer mouse model

Colorectal cancer (CRC) is the third most common cancer globally and the second leading cause of cancer-related deaths. Its pathogenesis involves dynamic interactions within the tumor microenvironment (TME), influencing tumor development. The TME comprises a diverse array of cell types and extracellular matrix (ECM) components that collectively form the tumor "tissue." Among them, innate immune cells are highly represented, with tumor-associated macrophages (TAMs) being the most abundant. TAMs acquire different profiles in response to environmental stimuli. In the TME, they obtain immunosuppressive functions, promoting tumor growth. Our findings revealed a link between TAMs and the immune receptor CD300e, highlighting a role in impairing macrophages’ antigen presentation. The immune receptor CD300e, selectively expressed on mature myeloid cells, downregulates antigen-presenting MHC II molecules in macrophages and is significantly upregulated in CRC patients. This study aims to understand CD300e's role in shaping the TAM profile, applying a constitutive CD300e knockout mouse subcutaneous model of CRC. Through immunophenotypic and molecular analysis, our findings disclose that CD300e deficiency ameliorates tumor development, evidenced by smaller tumors and increased infiltration of TAMs and T cells with immunostimulatory activity in CD300e KO mice. Our data suggest that CD300e deficiency in macrophages contributes to the development of anti-tumor immunity.