Change in MMR status as a mechanism of acquired resistance to immunotherapy in a dMMR colorectal cancer

While microsatellite instability-high (MSI-H) colorectal cancer (CRC) exhibits high sensitivity to immunotherapy, microsatellite stable (MSS) CRC is a particularly immune-resistant disease. Whether microsatellite status remains unvaried in solid tumours or changes over time under treatment pressure is largely unknown, as, to our knowledge, no previous cases have been reported in the literature.Here, we report the case of a patient with MSI-H CRC who experienced a long-lasting complete response to first-line pembrolizumab, but subsequently relapsed after more than 4 years with an MSS phenotype, which acts as an immune escape mechanism. This case may present new challenges in this field that have not been previously described.