Over the past 30 years, several studies on EAC patient cohorts consistently have shown a significant correlation between patient mortality and the lack of tumor-infiltrating CD8+ T cells and NK cells.156, 157, 158 Recent evidence has shown that this may be owed to the promotion of immunotolerance by an enrichment of inhibitory T-regulatory cells in more advanced tumors, and the possible mechanism by which inhibitory T-regulatory cells promote immunotolerance is through programmed cell death protein 1–mediated apoptosis of CD8+ T cells (Figure 3).105. This evidence concerns the gene CD8A and neoplasm.