Fig. 5: Immune metabolites of tumor cells affect the tumor micro-environment.

Tumor cells generate ROS and other metabolites that facilitate the differentiation and proliferation of immune cells toward pro-tumorigenic phenotypes within the tumor microenvironment, while simultaneously suppressing the anti-tumor functions of specific immune cell populations, ultimately leading to immune evasion. Through metabolic reprogramming, neoplastic cells deplete critical nutrients including glutamine and arginine to produce glutamate, which induces the differentiation of TAMs and DCs into M2-polarized macrophages and DCregs. Hypoxia-induced alterations in the TCA cycle result in excessive lactate and CO₂ production by tumor cells. Concurrently, ROS-mediated signaling promotes T cell differentiation into immunosuppressive regulatory T cells and T helper 2 (Th2) cells. Furthermore, tumor-derived fatty acids in abundance significantly impair the release of anti-cancer-related cytokines from natural killer (NK) cells²¹⁶.