The impact of hypoxia on immune state in cancer

Hypoxia is a known feature of solid tumors and a critical promoter of tumor hallmarks. Hypoxia influences tumor immunity in a way favoring immune evasion and resistance. Extreme hypoxia and aberrant hypoxia-inducible factor-1 (HIF-1) activity in tumor microenvironment (TME) is a drawback for effective immunotherapy. Infiltration and activity of CD8+ T cells is reduced in such condition, whereas regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) show high activities. Highly hypoxic TME also impairs maturation and activity of dendritic cell (DCs) and natural killer (NK) cells. In addition, the hypoxic TME positively is linked positively with metabolic changes in cells of immune system. These alterations are indicative of a need for hypoxia modulation as a complementary targeting strategy to go with immune checkpoint inhibitor (ICI) therapy.