CD47-mediated tumor microenvironment remodeling: a central mechanism in immune evasion

Immune evasion is a crucial strategy for tumor growth and survival, with the tumor microenvironment facilitating tumor immune evasion and cancer progression. CD47, a transmembrane protein highly expressed in various cancer cell types, interacts with its ligands SIRPα and TSP-1 to induce immune tolerance, enabling tumor cells to evade immune surveillance and phagocytosis by immune cells. Understanding the pathways driving CD47 signaling and related activation factors is essential. In this review, we discuss the interactions between CD47 and its ligands SIRPα and TSP-1; their roles in inhibiting the functions of immune cells (macrophages, dendritic cells (DCs), glial cells, T cells, NK cells, <i>etc</i>.); and the mechanisms involved. Furthermore, we also explore the influence of factors within the tumor microenvironment, including TNF-α, IFN-γ, ILs, HIF-1, oncogenes, isocitrate dehydrogenase 1, metabolic enzymes, and exosomes, on CD47-mediated immune evasion. Recent monoclonal antibody drugs targeting CD47 for cancer treatment have shown side effects and cause economic losses. Researchers can explore alternative approaches, such as designing targeted drugs with minimal side effects or investigating other related molecules or pathways. Combination therapy and further research into the molecular mechanisms of CD47 could offer new directions for antitumor drug development.