CoCl2-induced glioma hypoxia environment enhances CD47-SIRPα to promote tumor immune evasion

Elevated levels of tumor-associated macrophages and microglia in the immune microenvironment of malignant gliomas promote tumor growth and progression. Although immune evasion has been implicated in these processes, the mechanisms underlying the regulation of CD47-SIRPα-mediated immune evasion under hypoxic conditions remain unclear. Therefore, this study aimed to explore the mechanisms through which CD47-SIRPα modulates immune evasion in a cobalt chloride (CoCl₂)-induced hypoxic microenvironment of malignant gliomas. Human and mouse glioma cell lines were used to investigate immune evasion in vitro. After membrane protein extraction and nucleoplasmic isolation, we downregulated the expression levels of transport receptors to elucidate the regulation of CD47-SIRPα transport. The CoCl₂-induced hypoxic microenvironment attenuated microglial phagocytosis in glioma cells. Enhanced CD47-SIRPα interaction promoted immune evasion, which negatively affected tumor clearance. In addition, the intracellular transport of CD47 was promoted in the CoCl₂-induced hypoxic state. This process was regulated by regulator of chromosome condensation 1 (RCC1) and sortilin in the nuclear cytoplasm and cytoplasmic membrane, respectively. These results demonstrate the CD47-SIRPα-mediated immune escape mechanism of the CoCl₂-induced glioma hypoxic environment, which is associated with enhanced intracellular transport of CD47. Our findings provide a theoretical basis for the potential development of novel therapies targeting CD47-SIRPα.