Fig. 1.

Hypoxic stress impairs tumor cell susceptibility to cytotoxic T lymphocyte (CTL)-mediated lysis through induction of hypoxia-inducible factor (HIF)-1α, phosphorylated STAT3 (pSTAT3), and autophagy. Under hypoxia, tumor cells stabilize HIF-1α and activate pSTAT3, which renders them resistant to CTL-mediated lysis. Similarly, hypoxia-induced autophagy is responsible for the acquisition of resistance to CTL-mediated killing by selective degradation of pSTAT3 under autophagy inhibitions under hypoxia (78, 82).