IFNG and neoplasm: However, a major product of LDHA impedes the activation of NFAT in T cells and NK cells, reducing their ability to produce IFN-γ.177 Moreover, HIF-mediated regulation of vascular endothelial growth factor-A (VEGF-A) in CD8 + T cells accelerates tumor progression and disrupts vascular patterns, further emphasizing the role of HIF in shaping the TME.178 Notably, CD8 + T cells differentiate into a dysfunctional state, known as T-cell exhaustion, after persistent TCR stimulation in the TME.