Tumor‐derived mitochondrial formyl peptides suppress tumor immunity through modification of the tumor microenvironment

Mitochondrial N‐formylpeptides are released from damaged or dead cells to the extracellular spaces and cause inflammatory responses. The role of mitochondrial N‐formylpeptides in aseptic systemic inflammatory response syndromes induced by trauma or cardiac surgery has been well investigated. However, there are no reports regarding the role of mitochondrial N‐formylpeptides in cancer. In this study, we investigated the role of tumor cell‐derived mitochondrial N‐formylpeptides in anti‐tumor immunity using knockout murine tumor cells of mitochondrial methionyl‐tRNA formyltransferase (MTFMT), which catalyze N‐formylation of mitochondrial DNA‐encoded proteins. There was no apparent difference among the wild‐type and MTFMT‐knockout clones of E.G7‐OVA cells with respect to morphology, mitochondrial dynamics, glycolysis and oxidative phosphorylation, oxygen consumption rate, or in vitro cell growth. In contrast, in vivo tumor growth of MTFMT‐knockout cells was slower than that of wild‐type cells. A reduced number of myeloid‐derived suppressor cells and an increase of cytotoxic T‐lymphocytes in the tumor tissues were observed in the MTFMT‐knockout tumors. These results suggested that tumor cell‐derived mitochondrial N‐formylpeptides had a negative role in the host anti‐tumor immunity through modification of the tumor microenvironment. Tumor cell‐derived mitochondrial N‐formylpeptides had a negative role in the host anti‐tumor immunity through modification of the tumor microenvironment was suggested using knockout tumor cells of mitochondrial methionyl‐tRNA formyltransferase.