Microsatellite Instability (MSI) and Cancer — DNA Repair Failure, Neoantigens, and Immunotherapy Sensitivity

Microsatellite instability (MSI) is a genomic phenotype caused by failure of the DNA mismatch repair (MMR) system. When MMR is defective, short repetitive DNA sequences (microsatellites) accumulate insertion/deletion errors during replication

Direction of Regulation in Cancer: MMR function: DOWNREGULATED / LOST
MSI and Immunotherapy (Clinical Breakthrough)
MSI-high (MSI-H) tumors:
-Respond exceptionally well to PD-1/PD-L1 blockade
-Show durable responses across many tumor types

This led to the first tumor-agnostic approval of immunotherapy based on MSI status, regardless of tissue origin.

Clinical implication: MSI is a predictive biomarker for immunotherapy benefit.

MSI’s primary role is as a biomarker.