The increased PD-1-PD-L1 signaling (TAMs, cancer cells, and tolerogenic DCs express PD-1 and PD-L1), altered epigenetic reprogramming, and nutrient-deprived stressful TME through coordinating with the TCR signaling prove lethal to tumor-infiltrating CD8+T cells by altering their immunometabolic reprogramming (131, 327, 331, 332). Here, CD274 is linked to cancer.