PD-1 blockade is conventionally thought to increase the activity of CD8+ cytotoxic T-cells which interact with tumor antigen via MHC-I, however it has been found that HRS cells do not express MHC-I [94,95] suggesting anti-tumor immunity could be mediated by CD4+ effector cells via MHC-II antigen presentation [94]. This evidence concerns the gene CD4 and neoplasm.