Figure 1. Types of IFN insensitivity: primary and acquired.

Primary IFN insensitivity arises from mutations or epigenetic marks, leading to IFN-insensitive tumor cells. Acquired IFN insensitivity can be generated from tumors that initially respond to IFN but, as a result of clonal selection or phenotypic conversions, turn insensitive. Both types are driven and sustained by two forces of tumor evolution: tumor progression and immunoediting.