Scavenger Receptor CD36 Regulates Inflammatory and Type-I Interferon Responses in Tumor-Associated Macrophages

Abstract Macrophages are plastic cells of innate immune system with diverse functions in tissue homeostasis. Despite their abundance the tumor microenvironment (TME), tumor-associated macrophages (TAMs) and regulation mechanisms remain largely unknown. also key players metabolic processes including lipid metabolism. As TME has been known as a “lipid-rich” environment, we interested understanding how TAMs’ metabolism function regulated by receptors. In this research, firstly characterized phenotype TAMs mouse models. We found tolerogenic subset TAM (high expression F4/80 PD-L1) is lipid-laden greater ability to import lipids. hiTAMs highly express scavenger receptor CD36 which binds oxidized low-density lipoprotein (oxLDL) TME. Using myeloid-specific knockout (Cd36flox/floxx Csf1r-Cre) models, observed that CD36-deficient lost binding oxLDL, down-regulated immunosuppressive molecules PD-L1 CD206, while up-regulated secretion inflammatory cytokines (TNF, IL-12, IL-1b) IFNb. Overall, reprogrammed functional state leads better anti-tumor immunity. Mechanistically, conducted single-cell RNA-sequencing response type-I interferon pathways were TAMs. Furthermore, showed IFNb P38 play critical roles CD36-dependent regulations. summary, our data suggests plays reprogramming TAMs; blocking may have multi-faceted beneficial effects for future cancer immunotherapies. Supported fellowship from American Heart Association