Although it has been demonstrated that IFNs are critical in mounting anti-tumor response,49 emerging data suggested that IFN production from the cancer cells per se systemically represses the immune system.50–52 We found the mechanism that mitochondrial Lon-mtDNA–dependent IFN signaling suppresses CD8+ T-cell function is the induction of PD-L1 and IDO-1 expression. The gene discussed is CD8A; the disease is neoplasm.