Studies have demonstrated that IH exerts its immunosuppressive effects through various hypoxia-inducible factor-1a (HIF-1α)-related signaling pathways: inducing remodeling of the HIF-1α metabolic pathway and enrichment of lactate in the TIME; impeding T-cell proliferation, tumor invasion, and cytokine production; and augmenting myeloid-derived suppressor cell (MDSC) numbers while inhibiting natural killer (NK) cell and CD8+T cell activity (52). This evidence concerns the gene HIF1A and neoplasm.