Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 126, Issue 10, Pages 3689-3698Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI84430
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Funding
- NIH [CA148828, DK095201]
- T32 training grant Training in Basic and Translational Digestive Sciences [T32 DK 094775]
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The tumor immune response is in a dynamic balance between antitumor mechanisms, which serve to decrease cancer growth, and the protumor inflammatory response, which increases immune tolerance, cell survival, and proliferation. Hypoxia and expression of HIF-1 alpha and HIF-2 alpha are characteristic features of all solid tumors. HIF signaling serves as a major adaptive mechanism in tumor growth in a hypoxic microenvironment. HIFs represent a critical signaling node in the switch to protumorigenic inflammatory responses through recruitment of protumor immune cells and altered immune cell effector functions to suppress antitumor immune responses and promote tumor growth through direct growth-promoting cytokine production, angiogenesis, and ROS production. Modulating HIF function will be an important mechanism to dampen the tumor-promoting inflammatory response and inhibit cancer growth.
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