Further mechanistic studies revealed that IH can mediate significant immunosuppressive effects through multiple HIF-1α-dependent signaling pathways, including inducing lactate accumulation and metabolic pathway remodeling in the tumor immune microenvironment (TIME), inhibiting T cell proliferation and cytokine production, weakening T cell infiltration into tumor tissues, while promoting the expansion of myeloid-derived suppressor cells (MDSCs) and suppressing the antitumor functions of CD8+ T cells and natural killer (NK) cells (25). This evidence concerns the gene CD8A and neoplasm.