Liver metastases drive resistance to dual checkpoint blockade in metastatic colorectal cancer
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The phase II SERPENTINE trial tested dual PD-L1 and CTLA-4 blockade in patients with pMMR/MSS metastatic colorectal cancer, a population that typically does not respond to immunotherapy. The results, posted as a preprint on medRxiv Oncology, show a sharp split by metastatic site: patients without liver metastases derived clinical benefit from the combination, while every patient with liver metastases progressed. The findings point to site-specific immune remodeling, with the liver microenvironment emerging as a key determinant of resistance to dual immune checkpoint blockade. The data come from a preprint and have not yet appeared in a peer-reviewed journal; confirmation of the liver-metastasis effect in larger cohorts and whether the mechanism translates into strategies to overcome resistance remain open questions.
Written by a model from the reports · updated 5 hours ago
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- medrxiv.orgSite-specific immune remodeling underlies resistance to dual immune checkpoint blockade in metastatic colorectal cancer
The phase II SERPENTINE trial shows that after dual PD-L1 and CTLA-4 blockade in patients with pMMR/MSS metastatic colorectal cancer, those without liver metastases had clinical benefit, while all patients with liver metastases progressed.
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