A new class of cancer drugs called the immune checkpoint inhibitors (ICIs) (e.g. Keytruda) are making a transformative impact on the treatment of cancers, including that of bowel cancer. However, evidence suggests they will only work for a subset of patients unless better predictive biomarkers and cooperating drugs are identified. In a recently established and independent research programme, two robust and accessible markers for bowel cancer that correlate with disease progression, and which are expected to predict response to ICIs were identified. Moreover, the markers identify a further potential drug class that may increase the effectiveness of ICI therapy. In this study, the mechanism of the biomarkers will be clarified, the proposed combination therapy will be tested using disease models, and their potential translation to the clinic will be driven. In these studies, the is to expand the utility of ICIs to a larger number of bowel cancer patients.