Immune Checkpoint Inhibition in Metastatic Colorectal Cancer Harboring Microsatellite Instability or Mismatch Repair Deficiency

Romain Cohen; Raphaël Colle; Thomas Pudlarz; Maximilien Heran; Alex Duval; Magali Svrcek; Thierry André

doi:10.3390/cancers13051149

Immune Checkpoint Inhibition in Metastatic Colorectal Cancer Harboring Microsatellite Instability or Mismatch Repair Deficiency

Cancers (Basel). 2021 Mar 8;13(5):1149. doi: 10.3390/cancers13051149.

Authors

Romain Cohen^{1

2}, Raphaël Colle¹, Thomas Pudlarz¹, Maximilien Heran¹, Alex Duval², Magali Svrcek^{2

3}, Thierry André^{1

2}

Affiliations

¹ Department of Medical Oncology, Assistance Publique des Hôpitaux de Paris (AP-HP), Saint-Antoine Hospital, Sorbonne Université, F-75012 Paris, France.
² Centre de Recherche Saint Antoine, Équipe Instabilité des Microsatellites et Cancer, Équipe Labellisée par la Ligue Nationale Contre le Cancer et SIRIC CURAMUS, INSERM UMRS 938, Sorbonne Université, F-75012 Paris, France.
³ Department of Pathology, Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Sorbonne Université, F-75012 Paris, France.

Abstract

Microsatellite instability (MSI) is a tumor phenotype related to a deficient DNA mismatch repair system (dMMR). This phenotype, observed in 5% of metastatic mCRC but 10-18% of localized CRC, is associated with high tumor mutational burden with highly immunogenic neoantigens. It has emerged as a major predictive biomarker for the efficacy of ICIs. In this review, we will present a comprehensive overview of the literature concerning the efficacy of ICIs in MSI/dMMR mCRC, with a focus on new developments in first-line metastatic setting. Then, we will present current and future challenges of immuno-oncology for patients with MSI/dMMR metastatic CRC.

Keywords: Lynch syndrome; colorectal cancer; deficient mismatch repair; immunotherapy; microsatellite instability.

Publication types

Review