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Microsatellite instability (MSI) is currently the only biomarker predictive of immunotherapy efficacy in patients with metastatic colorectal cancer (mCRC). However, 10-40% of patients with MSI mRCC will experience primary resistance to immunotherapy.<\/p>\n
The work of C. Gallois et al (team 1), recently published in Clinical Cancer Research, has identified MSI CRC patients at risk of resistance to immunotherapy. Using previously published single-cell data, transcriptomic signatures of the tumor microenvironment were analyzed in 2 independent cohorts of 103 and 35 MSI CRC patients treated with immunotherapy. Three groups of patients with distinct transcriptional profiles reflecting different MET cell compositions and MET\/tumor cell proliferative capacities were identified:<\/p>\n
– group A (“stromalHIGH-proliferationLOW” )
\n– group B (“stromalHIGH-proliferationMED” )
\n– group C (“stromalLOW -proliferationHIGH”)<\/p>\n
Results showed a higher proportion of primary progression, significantly shorter progression-free survival and overall survival under immunotherapy in patients belonging to group A, compared with those belonging to groups B and C. In contrast, group A was not associated with poorer outcomes in patients treated with conventional chemotherapy.<\/p>\n
This classification could therefore help identify patients with MSI mRCC at risk of resistance to immunotherapy, in whom the therapeutic strategy could be adapted.<\/p>\n