Fig. 3.

EMP and ICB tumor-intrinsic resistance mechanisms. EMP may contribute to ICB resistance by modulating multiple tumor-intrinsic mechanisms, such as inducing increased autophagy, additional immune checkpoints, aberrant oncogenic/tumor suppressor signals, decreased sensitivity to IFN-γ and defects in antigen presentation. Their current research stages were annotated with the assigned colors. Blue stands for “unclear”, meaning further mechanistic work is needed; red stands for “rising topic”, meaning the mechanism is revealed or emerging; green stands for “correlated”, meaning the topic is related to EMP and immune resistance, but should be confirmed by more functional studies. β2M β2 microglobulin, CTLA-4 cytotoxic T-lymphocyte antigen-4, EMP epithelial mesenchymal plasticity, IRF1 interferon regulatory factor 1, LC3 microtubule-associated protein 1 A/1B-light chain 3, MAPK mitogen-activated protein kinase, MHC-I major histocompatibility complex I, OX40L tumor necrosis factor receptor OX40 ligand, PTEN tumor suppressor phosphatase and tensin homolog, PD-L2 programmed death-2 ligand, Snail snail family transcriptional repressor 1, TIM3 T-cell immunoglobulin and mucin domain-containing-3, TGF-β transforming growth factor β, WNT wnt family member protein