Fig. 4

Hypoxia-impaired susceptibility of tumor cells to effector-mediated killing. Under hypoxia conditions, tumor cells stabilize HIF-1α and activate pSTAT3, which renders them resistant to CTL-mediated lysis. Hypoxia-induced autophagy is responsible for the acquisition of resistance to CTL-mediated killing by inhibiting the degradation of pSTAT3. Similarly, in hypoxic tumor cells, excessive autophagy causes fusion of autophagosome with gigantosome to form amphisome. Subsequently, fusion of amphisome with lysosome triggers selective degradation of granzyme B, making hypoxic tumor cells resistant to NK cell-mediated killing