Microsatellite Instability: A Review of Molecular Epidemiology and Implications for Immune Checkpoint Inhibitor Therapy

SIMPLE SUMMARY: Microsatellite instability (MSI) occurs in a wide variety of tumor types and is one of the most important predictive biomarkers for immune checkpoint inhibitor therapy. The present review aims to summarize the molecular characteristics of MSI tumors as well as the results of major clinical studies evaluating the efficacy of checkpoint inhibitors in the treatment of patients with MSI tumors. ABSTRACT: Microsatellite instability (MSI) is one of the most important molecular characteristics of a tumor, which occurs among various tumor types. In this review article, we examine the molecular characteristics of MSI tumors, both sporadic and Lynch-associated. We also overview the risks of developing hereditary forms of cancer and potential mechanisms of tumor development in patients with Lynch syndrome. Additionally, we summarize the results of major clinical studies on the efficacy of immune checkpoint inhibitors for MSI tumors and discuss the predictive role of MSI in the context of chemotherapy and checkpoint inhibitors. Finally, we briefly discuss some of the underlying mechanisms causing therapy resistance in patients treated with immune checkpoint inhibitors.