Resistance to chemoimmunotherapy is a major issue for cancer care. We recently unravelled the role of mitogen-activated protein kinase (MAPK) to limit the antitumor efficacy of such combination. Inhibitor of MAPK pathway using mitogen-activated protein kinase (MEK) inhibitor in combination with chemotherapy triggers mitophagy of cancer cells, which induces the release of mitochondrial DNA that interact with Toll Like receptor 9 (TLR9) to promote the production of the chemokine CXCL10. CXCL10 could then turn cold tumor into hot tumor, thus leading to improve efficacy of chemoimmunotherapy.