Thus far, we have discussed activation and differentiation of T cells that lead to metabolic programming. Likewise, in the hostile envoirnment such as in the case of tumor, cellular metabolism reshape in ways that are central to T cells exhausation and at the same time Tregs sustainability. The tumor microenvironment poses metabolic hurdles such as hypoxia, low glucose, and high lactate concentration, meanwhile tumor cells require immune tolerance to evade host immunity. The upregulation of lactate impairs effector, and cytotoxic T cells function through LDH-mediated NAD depletion. However, Tregs resist this environment through FOXP3 expression [76], which acts as an intrinsic metabolic regulator that suppresses mTOR- and Myc- signaling pathways that activate- glycolysis while enhancing OXPHOS and NAD+/NADH generation and levels of FAO. These metabolic adaptations in Tregs allow them to sustain in severe inflammatory microenvironments without affecting their function, survival, and suppression, which is vital to maintain peripheral immune tolerance [56, 76, 77].  Additionally, tumor-infiltrating Tregs frequently display substantially upregulated expressions of co-inhibitory receptors, such as T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), lymphocyte activation gene 3 (LAG3), neuropilin 1 (NRP1), PD1, and CTLA4, to sustain stable FOXP3 activity, FOXO1 nuclear localization and higher levels of suppressive function [78].