Fig. 1

Immunoevasive signalling pathways in KRAS-mutant cancers. Immune evasion is mediated via MAPK pathway signalling enhanced by mutant KRAS, decreased type I/II IFN signalling, TTP inhibition, and co-mutations (e.g. STK11/KEAP1/TP53/EGFR). The effect of these pathway alterations is represented with cell-autonomous (e.g. increased survival and proliferation) and non-cell-autonomous programmes (e.g. decreased MHC expression, increased PD-L1 expression). Signalling through the TME to immune cells, via free and bound signalling molecules, and the immune evasive effects are also highlighted and attributed to specific signalling pathways (e.g. ICM suppression of CD8 + T cells, and reduced neoantigen detection due to PGE2). Immune cell metabolic reprogramming (IDO-1), increased pro-tumour cytokines and physical remodelling of the TME (MMP-9 and LOX), due to the KRAS signalling demonstrate its central role in tumour immune evasion. Treatments for abating these immune evasive mechanisms are shown. Arrows represent enhancement and flat heads represent inhibition, dotted lines are used to indicate inhibition by small molecule treatments, and red crosses represent pathways that have been blocked due to mutation or alterations in cell signalling