PRF1 and neoplasm: IFN-γ is a cytotoxic cytokine, which, together with granzyme B and perforin, initiates tumor cell apoptosis and enables the synthesis of immune checkpoint molecules such as PD-L1 and indoleamine-2,3-dioxygenase (IDO) to stimulate immune-suppressive mechanisms [27] Other studies have reported that IFN-γ production is regulated by natural killer (NK) and NK-T cells as part of the innate immunity, and during adaptive immune responses, CD8+ and CD4+ T cells are primary paracrine sources of IFN-γ [28].