Hypoxia: A Key Feature of the Tumor Microenvironment Triggers Several Mechanisms of Evasion from Natural Killer and Cytotoxic T Lymphocytes Surveillance

Since many years, the tumor microenvironment is recognized as an important promoter of cancer initiation and progression. Although tumors primarily consist in cancer cells, various components/factors of the microenvironment and more specifically the immune landscape, dramatically impact cancer progression. Comprehensive analyses conducted on diverse tumors have identified and characterized the most relevant components/ factors of the tumor microenvironment that support the malignant behaviorof a growing primary tumor. Tumor hypoxia is a common characteristic of the tumor microenvironment that is associated with tumor progression, metastasis, treatment failure and escape from immune surveillance. Although immune cells are usually efficiently recruited into the tumor bed, hypoxic microenvironment was reported to compromise immune cell functions and, in some cases, switch immune cell activity towards a pro-tumorigenic profile. Mechanistic studies have highlighted that hypoxia acts as double-edged sword: it simultaneously impairs the function of immune cells in the tumor microenvironment and activates intrinsic cell resistance mechanisms in tumor cells. The present article aims at reviewing some recent findings on how hypoxia impairs the anti-tumor immune response by focusing on emerging mechanisms by which hypoxia damps the function of immune effectors cells and activates intrinsic immune resistance mechanisms in tumor cells including autophagy and actin cytoskeleton remodeling.