Furthermore, in the present research study, multivariate analyses showed that only CD8+ and CD4+ remain the independent TILs associated with the checkpoints combined expression VISTA/CTLA4/PD1, and the mean counts of CD8+ and CD4+ TILS were higher in patients with VISTA+/CTLA4+/PD1+ positive expression, which suggests a paracrine mechanism used by cancer cells to communicate with the immune system by the expression of these negative checkpoints, as reported for PD-L1 in breast cancer patients (46, 47). This evidence concerns the gene PDCD1 and cancer.