Immune modulatory effects of oncogenic KRAS in cancer

Oncogenic KRAS mutations are the most frequent mutations in human cancer, but most difficult to target. While sustained proliferation caused by oncogenic KRAS-downstream signalling is a main driver of carcinogenesis, there is increasing evidence that it also mediates autocrine effects and crosstalk with the tumour microenvironment (TME). Here, we discuss recent reports connecting KRAS mutations with tumour-promoting inflammation and immune modulation caused by KRAS that leads to immune escape in the TME. We discuss the preclinical work on KRAS-induced inflammation and immune modulation in the context of currently ongoing clinical trials targeting cancer entities that carry KRAS mutations and strategies to overcome the oncogene-induced effects on the immune system. Oncogenic signalling has been historically associated with sustained cancer cell-intrinsic proliferation, however its role in promoting tumour immunoresistance has also become evident. Here, Hamarsheh and colleagues review and discuss the preclinical work on the immune modulatory effects of oncogenic KRAS and the potential clinical application.