Resistance to chemo-immunotherapy is a major issue for the treatment of non-small cell lung cancer. In a recent paper we unravel the role of MAPK in the capacity of restraining the therapeutic efficacy of chemo-immunotherapy. Inhibition of the MAPK pathway using a MAP2K/MEK inhibitor in combination with chemotherapy could promote OPTN (optineurin)-dependent mitophagy of cancer cells. Mitochondria then degrade via autophagosomes and amphisomes and release mitochondrial DNA, which interacts with TLR9 located in these compartments. TLR9 activation promotes the production of the chemokine CXCL10 by cancer cells, which could further improve T cell recruitment and improve the efficacy of immunotherapy.
Keywords: CXCL10; Chemotherapy; MAP2K/MEK inhibitor; TLR9; ULK1; immunotherapy; mitophagy; optineurin.