Prompted by the relatively short duration of tumor control following iterative administrations of anti-PD-1 mAb in tumor bearing mice, we identified a detrimental role of interferon-α/β receptor (IFNAR) signaling in both CD45− and CD45+ intratumoral subsets inducing the expression of nitric oxide synthase 2 (NOS2). Here, NOS2 is linked to neoplasm.