CD8A and breast cancer: Furthermore, in immunologically cold breast cancers (e.g., TNBC), mitochondrial complex I inhibitors (e.g., IACS-010759) synergize with TLR agonists (e.g., CpG-ODN) via the TIR-MyD88 pathway to upregulate NADPH oxidase activity in neutrophils, generating large amounts of ROS and enabling them to acquire tumor-killing capabilities independent of CD8+ T cells (102).