CD4 and neoplasm: However, it was reported that when CTLA-4 inhibitors were applied to such cold tumors, CD3+/CD4+ and CD3+/CD8+ T cells could be recruited and even fully activated to increase the infiltration of lymphocytes in the tumor microenvironment and upregulate INF-γ, thereby up-regulating the expression of PD-L1 to resensitize the tumor cells to PD-1 inhibitors (Wei et al., 2017; Wu et al., 2019; Rupp et al., 2022).