Fig. 2.

Graphical summary that explains underlying mechanism of acquired resistance to ICIs in terms of tumor cell-intrinsic and tumor cell-extrinsic factors. Tumor intrinsic mechanisms of acquired resistance involve loss of immunogenic antigens, defects in antigen processing and presentation, and mutations of IFN‐γ/JAK signaling pathway. Tumor extrinsic mechanisms of acquired resistance mainly include activation of alternate inhibitory immune checkpoints, immunosuppressive tumor microenvironment, epigenetic modification, and dysbiosis of the gut microbiome