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The impact of hypoxia on immune state in cancer

Journal

LIFE SCIENCES
Volume 286, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.120057

Keywords

Hypoxia; Hypoxia inducible factor (HIF); Immune checkpoint inhibitor (ICI); Tumor microenvironment (TME); Dendritic cell (DC); CD8(+) T cell; Natural killer (NK)

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Hypoxia in the tumor microenvironment plays a significant role in suppressing the infiltration and activity of CD8(+) T cells, while enhancing the activities of regulatory T cells and myeloid-derived suppressor cells. This hypoxic environment also impairs the maturation and function of dendritic cells and natural killer cells, highlighting the importance of modulating hypoxia as a complementary strategy to immune checkpoint inhibitor therapy.
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.

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