Thus, our results indicate that the combination of antimetabolic chemotherapeutics (eg, pemetrexed) with PD-1/PD-L1 blockade (eg, anti-PD-L1 antibody) could further enhance the antitumor immune responses and restore exhausted T-cell activities, thereby priming a favorable tumor microenvironment for cancer immunotherapy. The gene discussed is CD274; the disease is cancer.