CTLA-4 interacts with CD80/CD86, inhibiting T cell stimulation and IL-2 and IL-12 synthesis122 PD-1+ CTLA-4+ CD8+ TILs have been more adversely exhausted in proliferation and cytokine synthesis as PD-1 and CTLA-4 are co-expressed in one-third or half of the CD8+ TILs, but combined inhibition of PD-1 and CTLA-4 improves T cell activity in cancer [Figure 4].123. This evidence concerns the gene CTLA4 and cancer.