Journal
JOURNAL OF SURGICAL ONCOLOGY
Volume 123, Issue 3, Pages 760-774Publisher
WILEY
DOI: 10.1002/jso.26357
Keywords
checkmate; checkpoint blockade; keynote; microsatellite instability; mismatch repair deficiency
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Immune checkpoint inhibition has shown high efficacy in colorectal cancer with mismatch-repair deficiency, while the response is poor in cases with preserved MMR/microsatellite stability. Besides studying the application of ICI in dMMR/MSI-H mCRC, attention should also be paid to its role in locally advanced disease, response biomarkers, and future targets.
Immune checkpoint inhibition (ICI) has transformed the management of metastatic colorectal cancer (mCRC) with mismatch-repair deficiency (dMMR) and microsatellite instability (MSI-H), though this constitutes on average less than 5% of mCRC, and ICI is ineffective in preserved MMR/microsatellite stable disease (pMMR/MSS). Here we review the efficacy of ICI in dMMR/MSI-H mCRC, poor response to ICI in pMMR/MSS mCRC, role for ICI in locally advanced disease, biomarkers of response, novel immunotherapies, and future directions in targeting resistance mechanisms.
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