CD274 and neoplasm: Ionizing radiation has been shown to upregulate PD-1/PD-L1 expression in the tumor microenvironment, but its effect on the biology of latent second primary tumors has remained unclear.37 Recent research has revealed high frequency of colocalization of CD4-positive tumor-infiltration lymphocytes and PD-1 and in OCSCC.38 These CD4-positive, PD-1–positive T cells were shown to be anergic in the setting of PD-L1 expression and, hence, contributed to the immunosuppressive tumor microenvironment of OCSCC.