MSI-H is one of the strongest predictors of response to pembrolizumab - and uniquely, it can qualify patients for treatment regardless of their cancer type. Understanding what it means, and whether your tumour has been tested for it, could be important for your treatment options.
What is microsatellite instability?
Microsatellites are short, repetitive sequences of DNA scattered throughout the genome. In healthy cells, a system of proteins called the mismatch repair (MMR) system corrects errors that accumulate in these regions during cell division. When the MMR system is defective - either due to inherited mutations (as in Lynch syndrome) or acquired changes within the tumour - errors are not corrected and accumulate. This leads to microsatellite instability: the lengths of microsatellite sequences vary between the tumour and normal tissue.
MSI-H (microsatellite instability-high) means a high level of this instability is present. The equivalent term from protein testing is dMMR (deficient mismatch repair) - the two reflect the same underlying problem detected by different laboratory methods.
Why MSI-H predicts immunotherapy response
Tumours with defective mismatch repair accumulate a very large number of mutations. These mutations generate abnormal proteins - neoantigens - that the immune system can potentially recognise as foreign. MSI-H tumours are therefore highly immunogenic: they have many potential targets for T cell attack. When pembrolizumab removes the PD-1 brake, the immune system has a rich set of targets to respond to. This is why response rates to pembrolizumab in MSI-H tumours are substantially higher than in microsatellite-stable (MSS) tumours.
The pan-tumour approval
Pembrolizumab was the first cancer drug to receive a tumour-agnostic approval - meaning it was approved for any solid tumour with MSI-H or dMMR status, regardless of where in the body the cancer originated. This was based on data from KEYNOTE-158, which enrolled patients across multiple tumour types and demonstrated consistent, durable responses in MSI-H disease. For patients with MSI-H colorectal cancer, cervical cancer, endometrial cancer, or other tumour types, this approval opens an immunotherapy option that PD-L1 expression alone might not.
How is MSI/MMR status tested?
Testing is performed on tumour tissue. MMR status can be assessed by immunohistochemistry (IHC), which looks for loss of the MMR proteins (MLH1, MSH2, MSH6, PMS2). MSI status can also be assessed by PCR or next-generation sequencing, which directly measures the stability of microsatellite sequences. Both methods are available through NHS and private laboratory services.
Do you know your MSI or MMR status?
Our eligibility check includes biomarker questions. An oncologist reviews every submission within 24 hours and can advise on eligibility based on MSI-H status.
Check your eligibility