Fig. 4.

Metabolic reprogramming of immune cells and their altered functions to cancer cells. A) Metabolic shift in tumor-associated macrophages (TAMs) at tumor onset and during progression. At tumor onset, a glycolytic shift, activation of HIF1α, and inhibition of oxidative phosphorylation (OXPHOS) induce the expression of NO, ROI, and inflammatory cytokines such as IL-1β and TNF in inflammatory macrophages to support cancer-related inflammation and genetic instability that leads to tumorigenesis. At established tumors, nutrient deprivation-induced AMPK activation, Th2-derived IL-4 (which activates STAT6, p53, c-Myc, and PGC1β), lactate accumulation, and PKM2 activation suppress glycolysis in TAMs while upregulating OXPHOS. This metabolic change induces immunosuppressive TAMs that promote tumor growth. Changes in the metabolism of iron, amino acid, and fat that contribute to this process are also shown