When Cells Suffocate: Autophagy in Cancer and Immune Cells under Low Oxygen

Figure 2

Proposed roles for hypoxia-induced autophagy in APCs. During low oxygen HIF-1α initiates TLR4 transcription [102]. TLR4 can then be engaged by HMGB1 (high-mobility group box-1 protein), a danger-associated molecular pattern molecule released from dying tumor cells after chemotherapy or radiation resulting in activation of the APC [103]. The engagement of TLR4 results in signalling through adaptor molecules MyD88 (myeloid differentiation primary response gene 88) and TRIF (TIR-domain-containing adapter-inducing interferon-β) which both inhibit the interaction of Bcl-2 with Beclin 1 to induce autophagy [64, 65]. Autophagy can then aid in processes such as improved phagosomal degradation and MHC presentation of tumor antigens for activation of the immune response [66, 67].