Fig. 4

Illustrates the mechanisms of metabolic regulation in tumor immune evasion. Tumor cells and immune cells adapt to the tumor microenvironment by modifying their metabolic programs in response to conditions such as hypoxia and nutrient deprivation. a Tumor oncogenic signaling pathways and transcription factors play a crucial role in regulating the expression of immune checkpoint molecules and genes associated with glycolysis, ultimately contributing to tumor immune evasion. Additionally, metabolites can directly influence the expression of immunosuppressive molecules. b Dysfunctions in immune cells may arise due to alterations in metabolites. The upregulation of glycolysis in tumor cells affects the expression levels of MHC-I and PD-L1 proteins, while glucose deprivation and increased lactate levels inhibit the function of NK and CD8⁺ T cells but enhance the suppressive activity of Treg cells within the tumor microenvironment. c A competition in glutamine metabolism is observed in the tumor microenvironment, where enhanced arginine-sensing mechanisms support the survival of T cells. Furthermore, lactate produced by tumors can induce macrophages to shift towards the M2 phenotype, potentially leading to arginine deprivation in T cells and NK cells. d Tumor immune cells display distinct metabolic characteristics, with Treg cells and M2 macrophages maintaining their suppressive function facilitated by fatty acid transporters like CD36, while the presence of fatty acids hinders the effector function and viability of CD8⁺ T cells. In this context, black arrows represent promotion, while black bars symbolize inhibition. This figure was created using Figdraw