Tumor hypoxia: a key player in the regulation of stromal and anti-tumor responses

Hypoxia is a major feature of most solid tumors. Cells adapt to lower oxygen availability by stabilizing HIF transcription factors, which in turn activate the expression of many genes resulting in the survival and maintenance of cellular functions. In tumor cells, exposure to hypoxic stress results in the activation, via the HIF factors, of a series of genes enabling tumor cells to resist to killing by cytotoxic effectors of the immune system. Tissue hypoxia also controls the functions and differentiation of immune cells. This review describes the hypoxia-induced mechanisms of tumor resistance to killing by cytotoxic effectors, and the functional effects of hypoxia on the immune cells.