Given the emerging intrinsic roles of PD-L1 and PD-1 and the differences between cancer types, utilizing models which closely mimic the heterogeneity of the human tumor microenvironment could allow a more predictive in vitro evaluation of the intrinsic role of PD-L1 and PD-1 in cancer and modulation by anti-cancer therapeutics. The gene discussed is CD274; the disease is cancer.