The Role of Hypoxia in the Tumor Microenvironment: Implications for Ovarian Cancer Therapy
Technical Report,01 Jul 2015,30 Jun 2016
Leland Stanford Junior University Palo Alto United States
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Hypoxia is a potent microenvironmental factor promoting metastatic progression. A critical step in metastatic tumor progression is the ability of tumor cells to evade immune attack. Tumor cells utilize a complex set of mechanisms that prevent the immune system from mounting effective anti-tumor responses. Moreover, the hypoxic tumor microenvironment plays an important role in immune escape by favoring immune suppression and tumor resistance. Tumor hypoxia is thought to promote the immunosuppressive phenotypes of both tumor cells as well as infiltrating immune cells. However, the mechanisms by which hypoxia promotes immunosuppression in ovarian cancer remains to be elucidated and may have important therapeutic implications in the treatment of metastatic ovarian cancer. We hypothesize that hypoxia through HIF-1 signaling in regulatory T cells promotes angiogenic and immunosuppressive phenotypes, each contributing to metastatic ovarian cancer tumor growth. Here we generated mice to directly assess the functional role of HIF-1 in Treg cells in ovarian cancer metastatic tumor growth, angiogenesis, and immunosuppression.
- Medicine and Medical Research