CD28 and cancer: Interestingly, many immune checkpoint genes, which are established or promising targets for immune checkpoint blockade therapy, had significantly higher expression levels in the higher-TMB subtype of various cancers, such as CTLA4, PD-1, PD-L1, PD-L2, LAG3, IDO1 and TIGIT. In contrast, 16 immune checkpoint genes (C10orf54, CD200, CD40LG, ADORA2A, TNFSF14, BTLA, CD160, CD44, CD48, CD28, VTCN1, CD200R1, NRP1, TMIGD2, ICOS, and TNFSF15) had significantly higher expression levels in the lower-TMB subtype than in the higher-TMB subtype of at least 6 cancer types.