To understand the underlying mechanisms responsible for the NANOG-driven immune-refractory feature of the TME in ICB therapy, we conducted 3 rounds of in vivo selection following PD-1 blockade to establish new anti–PD-1 therapy–refractory tumor models from a CT26 cell line (designated as CT26 P0 cells) or a YUMM2.1 cell line (designated as YUMM2.1 P0 cells), both of which have frequently been used as preclinical tumor models for the study of cancer biology and tumor immunology as well as evaluating the efficacy of ICB therapy (Supplemental Figure 3 and refs. 36–39). Here, NANOG is linked to neoplasm.