From a teleological point of view, such genetic events may be selected to circumvent the cytostatic and/or cytotoxic effects of IFNs.23,26 However, in contrast to loss-of-function resistance mechanisms, adaptive resistance could be viewed as a negative feedback loop dulling anti-tumor T cell activity through functional IFN receptor signaling pathways, resulting in the upregulation of immunosuppressive PD-L1 or galectins47 or NOS2 as exemplified here. The gene discussed is NOS2; the disease is neoplasm.