Current efficacy of immune checkpoint inhibitors in microsatellite unstable colorectal cancer and potential biomarkers

Abstract

Microsatellite unstable (MSI) colorectal cancer (CRC) tumors have a high mutational load (particularly frame-shift mutations) that creates numerous neoantigens that are presented to major histocompatibility complex molecules and recognized by T cells. Consequently, MSI tumors have a higher presence of tumor-infiltrating lymphocytes than mismatch repair-proficient tumors. Colorectal cancer patients with MSI constitute a rare group of immune checkpoint inhibitor (ICI)-responsive patients. Nonetheless, complete radiological responders comprise between 3% and 16% of MSI advanced CRC patients, which compares poorly with the 45% to 87% rate of pathological complete response in early MSI CRC patients treated with ICIs. In this review, we address the efficacy of current ICIs and the biological differences between early and advanced MSI CRC to potentially increase the efficacy of ICIs in both settings.