From clusters to clinic: An 8-gene signature combined with mucinous component stratifies benefit of anti-CTLA-4 addition to anti-PD-1 in dMMR/MSI-H metastatic colorectal cancer
BACKGROUND: ) associated with the shortest PFS. Here we combine gene signature and mucinous phenotype to predict the benefit from anti-CTLA-4 plus anti-PD-1. METHODS: (A vs B/C) with mucinous component (present vs absent). RESULTS: A + mucinous (25/163, 15.3%) derived advantage from Combo versus Mono: adjusted 24-month PFS 72.2% vs 13.8% (HR 0.10, 95% CI 0.02-0.39; p < 0.001). CONCLUSIONS: An 8-Gene signature combined with mucinous component identifies a subgroup that preferentially benefits from anti-PD-1 +CTLA-4, warranting prospective validation to guide regimen selection in dMMR/MSI-H mCRC.
Authors
- Emily Linda Alouani (ORCID: https://orcid.org/0000-0002-2303-118X)
- Janick Sèlves (ORCID: https://orcid.org/0000-0001-6122-7004)
- Claire Gallois (ORCID: https://orcid.org/0000-0003-2369-7341)
- Annalice Gandini (ORCID: https://orcid.org/0000-0003-2873-5108)
- Francesca Bergamo (ORCID: https://orcid.org/0000-0002-8795-4653)
- Thibault Mazard (ORCID: https://orcid.org/0000-0002-5644-9603)
- S. Mouillet-Richard
- Julien. Taïeb
- Aurélie Lecanu
- Pierre Laurent-Puig
- Margherita Ambrosini
- Sara Lonardi
- Filippo Pietrantonio
- Chiara Cremolini
- Rosine Guimbaud
- Jean-Francois Emile
- David Tougeron
Institutions
- University of Pisa (IT)
- Université de Tours (FR)
- Délégation Paris 5 (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université de Montpellier (FR)
- Université Paris Cité (FR)
- Université Paris-Saclay (FR)
- Centre Hospitalier Universitaire de Toulouse (FR)
- Université de Poitiers (FR)
- Sorbonne Université (FR)
- Sorbonne Paris Cité (FR)
- Centre de Recherche des Cordeliers (FR)
- Centre Hospitalier Universitaire de Tours (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Hôpital Européen Georges-Pompidou (FR)
- Istituto Oncologico Veneto (IT)
- Hôpital Rangueil (FR)
- Hôpital Ambroise-Paré (FR)
- Institut de Recherche en Cancérologie de Montpellier (FR)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (FR)
Publication Details
- Journal
- European Journal of Cancer
- Published
- 2026-04-06
- DOI
- https://doi.org/10.1016/j.ejca.2026.116731
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Gilead Sciences
- Merck KGaA
- Jazz Pharmaceuticals
- Les Laboratories Pierre Fabre
- BeiGene
- Incyte
- Advanced Accelerator Applications
- Seagen
- Natera
- Daiichi-Sankyo
- Fondation ARC pour la Recherche sur le Cancer
- Astellas Pharma
- Shionogi
- Institut National Du Cancer
- Servier
- Ono Pharmaceutical
- Ipsen
- Italfarmaco
- Nordic Pharma Group
- Genentech
- Daiichi Sankyo Europe