CD36 and Its Role in Regulating the Tumor Microenvironment

Abstract

CD36 is a transmembrane glycoprotein that binds to a wide range of ligands, including fatty acids (FAs), cholesterol, thrombospondin-1 (TSP-1) and thrombospondin-2 (TSP-2), and plays an important role in lipid metabolism, immune response, and angiogenesis. Recent studies have highlighted the role of CD36 in mediating lipid uptake by tumor-associated immune cells and in promoting tumor cell progression. In cancer-associated fibroblasts (CAFs), CD36 regulates lipid uptake and matrix protein production to promote tumor proliferation. In addition, CD36 can promote tumor cell adhesion to the extracellular matrix (ECM) and induce epithelial mesenchymal transition (EMT). In terms of tumor angiogenesis, CD36 binding to TSP-1 and TSP-2 can both inhibit tumor angiogenesis and promote tumor migration and invasion. CD36 can promote tumor angiogenesis through vascular mimicry (VM). Overall, we found that CD36 exhibits diverse functions in tumors. Here, we summarize the recent research findings highlighting the novel roles of CD36 in the context of tumors.

Keywords: CD36; angiogenesis; lipid metabolism; tumor-associated immune cells.

Figure 1

CD36 primary structure. The CLESH structural domain in CD36 can regulate tumor angiogenesis by interacting with the TSR. CD36 forms two hydrophobic lumens (entrance 1 and entrance 2) in its pericyte region and binds to hydrophobic lipid-associated proteins to regulate cellular lipid metabolism.

Figure 2

CD36 plays a role in tumor immunity. CD36 mediates Ox-LDL uptake, promotes lipid peroxidation in CD8⁺T cells, phosphorylates p38 kinase, which in turn inhibits IFN-γ and TNF production. CD36 also activates PPAR-β signaling to enhance mitochondrial fitness of Treg cells in tumors. And CD36 promotes STAT6 phosphorylation to enhance mitochondrial fitness of TAMs, which in turn promotes tumor proliferation.