Immunotherapy for Microsatellite-Stable Metastatic Colorectal Cancer: Can we close the Gap between Potential and Practice?

Abstract

This review will explore various strategies to rendering MSS mCRCs susceptible to ICI. Moreover, we will provide an overview of potential biomarkers that may aid to better patient selection, and discuss ongoing efforts in this area of research. Colorectal cancer (CRC) ranks among the top three most common cancers worldwide. While significant advances in treatment strategies have improved the prognosis for patients in the early stages of the disease, treatment options for metastatic CRC (mCRC) remain limited. Although immune checkpoint inhibitors (ICI) have revolutionized the treatment of several malignancies, its efficacy in mCRC is largely confined to patients exhibiting a high microsatellite instability status (MSI-H). However, the vast majority of mCRC patients do not exhibit a MSI-H, but are microsatellite stable (MSS). In these patients ICIs are largely ineffective. So far, ICIs do not play a crucial role in patients with MSS mCRC, despite the promising data for inducing long-term remissions in other tumour entities. For this reason, novel treatment strategies are needed to overcome the primary resistance upon ICI in patients with MSS.