Mucinous histology and resistance to immune checkpoint blockade in patients with microsatellite instability-high metastatic colorectal cancer
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Mucinous phenotype has been associated with an immune-cold microenvironment in dMMR/MSI-H CRC. Here, we investigated the impact of mucinous histology on resistance to ICIs in patients with dMMR/MSI-H mCRC. PATIENTS AND METHODS: We collected data on patients with dMMR/MSI-H mCRC receiving anti-PD-1 alone or with anti-CTLA-4 agents in any line from a multinational dataset. Mucinous histology was defined locally as ≥50% mucinous component. The occurrence of progression or death of disease within or after 6 months from ICIs initiation were considered innate (IR) and acquired resistance (AR). Progression-free survival (PFS)-1 and overall survival (OS)-1 were calculated using the 6-month landmark from the start of ICIs in patients without IR. RESULTS: Among 929 patients, 316 (34%) had mucinous tumors and had inferior PFS and OS. At a median follow-up of 44.7 months, the 6-month PFS rate was similar in patients with mucinous and non-mucinous tumors (71.5% and 73.0%) and a subsequent divergence of the PFS and OS curves was observed beyond this timepoint. In patients without IR, mucinous histology was independently associated with shorter PFS-1 (multivariable model HR 2.10, 95%CI 1.56-2.82; p < 0.001), while OS-1 was non-significantly shorter (HR 1.36, 95%CI 0.91-2.02, p = 0.130). Dual anti-CTLA4/PD-1 blockade was associated with longer PFS and OS regardless of mucinous histotype, but the worst outcomes were observed in patients with mucinous histology receiving single-agent anti-PD-1 (3-year PFS and OS: 39.7% and 56.1%). CONCLUSION: Mucinous histology is associated with ICIs resistance, particularly AR, in dMMR/MSI-H mCRC. These findings may be useful to guide the management of this disease in practice.
Source: The Oncologist
Authors: Vincenzo Nasca, Margherita Ambrosini, Julien Taieb, Romain Cohen, Sara Lonardi, Ben Boursi, Ofer Margalit, Lisa Salvatore, Javier Ros, Giovanna Sabella, Chiara Rossi, David Tougeron, Rosine Guimbaud, Claire Gallois, Maria Elena Elez, Francesca Bergamo, Chiara Cremolini, Michael J Overman, Thierry André, Giovanni Randon, Filippo Pietrantonio
Institutions: Fondazione IRCCS Istituto Nazionale dei Tumori, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Inserm, Sorbonne Université, La Ligue Contre le Cancer, Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine, Istituto Oncologico Veneto, Tel Aviv University, Sheba Medical Center, Università Cattolica del Sacro Cuore, Agostino Gemelli University Polyclinic, Vall d'Hebron Hospital Universitari, Centre Hospitalier Universitaire de Poitiers, Hôpital Rangueil, Azienda Ospedaliera Universitaria Pisana, The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,852
OpenAlex ID: W7154392931