Table 1.

Summary of TME mediated modulation of immunometabolism.

TME Factors Affecting Immune Cell Metabolism	Direct and Indirect Metabolic Impairment of Immune Cells in TME	Strategy to Overcome Induced Metabolic Impairment	References
Increased hypoxia	Increases HIF1-a and PD-L1 on MDSCs for T cell exhaustion and Treg generation	Anti-PD-L1 and HIF inhibitors	[43,69,70]
Increased reactive oxygen species	Oxidative stress-mediated inhibition of NF-kB or mTOR for the prevention of T cell activation	Catalase, an antioxidant enzyme	[32,42]
Decreased glucose availability	Reduced AKT, mTOR, GLUT1, phosphoenolpyruvate, and increased PD-1 expression in T cells	anti-PD-1, anti-PD-L1, anti-CTLA-4	[27,46,48,49,50]
Increased lactate	Inhibition of T cell glycolysis and function	Blocking acidification prior to anti-PD-1 or anti-CTLA-4 administration	[52]
Low levels of arginine	Reduced responsiveness of T cells due to decreased expression of CD3ζ chain	Administering arginine	[55,56]