Colon cancer and immunotherapy—can we go beyond microsatellite instability?

Immune checkpoint blockade (ICB) has changed the landscape of cancer therapy in multiple tumor types since the first agent, Ipilimumab, was first FDA approved for the treatment of metastatic melanoma in 2011. Its role in GI Cancers, particularly in colon cancers, has not been as robust as in other tumor types but select patients with DNA mismatch repair defects, even those who has progressed on multiple standard chemotherapeutic regimens have demonstrated significant, almost unprecedented, responses in this multidrug refractory population. Unfortunately, these cases represent only a small percentage of colon cancer patients with little efficacy in the 95% of metastatic colon cancers who have proficient DNA mismatch repair. Multiple strategies have been, and are currently being, evaluated to determine the potential benefits of this drug class to microsatellite stable (MSS) patients.