Potential utility of more subtle microsatellite instability for predicting response to nivolumab in gastric cancer patients

The relationship between microsatellite instability (MSI) - high (H) and deficient DNA mismatch repair is, in fact, not straightforward. MSI observed in genome-edited cells carrying Lynch syndrome mutations is not so drastic as in typical MSI-H ( i.e. Type B mode) but uniformly more subtle ( i.e. Type A mode). In our preceding study, we demonstrated a tight connection between the more subtle mode of MSI, i.e. Type A MSI, and 5-FU resistance in colorectal cancer patients. In this study, we tested if Type A MSI is similarly useful to predict tumour sensitivity to immune checkpoint inhibitors (ICIs). In thirty-eight gastric cancer patients treated with nivolumab monotherapy, eleven ‘good responders’ and eight ‘poor responders’ were selected according to iRECIST and enrolled. In them, Type A MSI was indeed observed, and seven patients were judged as Type A-positive. More importantly, Type A MSI was significantly more frequent in ‘good responders’ than in ‘poor responders’ (7/11 vs 0/8, p = 0.013). Our findings in this pilot cohort may shed light on the potential utility of more subtle Type A MSI to predict response to ICIs in cancer patients.