NOS2 and neoplasm: Finally, when considering RT as a response modifier of IO, low-dose irradiation (LDI) with one or a few fractions of 0.5 to 2 Gy has been shown to potentially increase the immunogenicity of “cold tumors” through several mechanisms: preferential induction of T-reg apoptosis compared with effector T cell cells (40); skewing macrophages from an M2 phenotype (promoting tumor growth) towards an inducible nitric oxide synthase-positive (iNOS+) M1 phenotype.