Abstract 297: Effect of hypoxia on the expression of the T cell co-inhibitory ligands B7-H3 and B7-H1 in cancer

Abstract

Abstract Escape from adaptive immunity is important for malignant progression. B7-H3 and B7-H1 ligands provide co-inhibitory signals to T cells resulting in T cell anergy or apoptosis. Their expression has been shown to increase in cancer cells and to correlate with disease progression. Tumour hypoxia is a major contributor to the spread of cancer and resistance to radiation and chemotherapy. We proposed that hypoxia results in the up-regulation of the B7 molecules B7-H3 and B7-H1, thus contributing to immune escape. Using breast and prostate cancer cell lines, we investigated whether hypoxia increases the expression of these ligands and, if so, whether the transcription factor hypoxia-inducible factor-1 (HIF-1) is required for this hypoxic effect. We incubated MDA-MB-231 breast cancer cells and DU145 prostate cancer cells in standard culture conditions (20% O2, 37°C, 5% CO2), hypoxic conditions (0.5% O2, 37°C, 5% CO2), or with 100μM CoCl2 (known to stabilize HIF-1α) for 24 hours. Our findings revealed that B7-H3 expression is not increased in hypoxia. However, hypoxia and exposure to CoCl2 increased B7-H1 expression, which correlated with the levels of HIF-1α accumulation. Furthermore, HIF-1α knockdown attenuated B7-H1 mRNA levels. These results indicate a role for hypoxia in the up-regulation of B7-H1 on cancer cells, thus potentially contributing to immune escape of cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 297. doi:1538-7445.AM2012-297