CD28 and hepatocellular carcinoma: Multiple immune cell differences were differentially expressed between the two CRGs subtypes, such as T regulatory cells, macrophages, monocytes, etc. We also discovered there was a significant association between immune checkpoints and CRGs, most notably PDCD1 (PD-1), TIGIT, CTLA4, ICOS, BTLA, CD28, LAG3, and CD27. Previous studies demonstrated that the combination of immune checkpoint inhibitors (ICIs) and bevacizumab showed superiority over sorafenib in unresectable HCC (Finn et al., 2020)- (Ren et al., 2021), which was consistent with the mechanism of immune checkpoints.