{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:59:17Z","timestamp":1791377957191,"version":"4.3.2"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>We collected data on patients with dMMR\/MSI-H mCRC receiving anti\u2013PD-1 alone or with anti-CTLA-4 agents in any line from a multinational dataset. Mucinous histology was defined locally as \u226550% mucinous component. The occurrence of progression or death of disease within or after 6\u2009months 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 929 patients, 316 (34%) had mucinous tumors and had inferior PFS and OS. At a median follow-up of 44.7\u2009months, 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\u20132.82; p\u2009&amp;lt;\u20090.001), while OS-1 was non-significantly shorter (HR 1.36, 95%CI 0.91\u20132.02, p\u2009=\u20090.130). 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%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag145","type":"journal-article","created":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T11:37:03Z","timestamp":1775907423000},"source":"Crossref","is-referenced-by-count":3,"title":["Mucinous histology and resistance to immune checkpoint blockade in patients with microsatellite instability-high metastatic colorectal cancer"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7897-402X","authenticated-orcid":false,"given":"Vincenzo","family":"Nasca","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4131-2409","authenticated-orcid":false,"given":"Margherita","family":"Ambrosini","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9955-4753","authenticated-orcid":false,"given":"Julien","family":"Taieb","sequence":"additional","affiliation":[{"name":"Department of Digestive Oncology, Georges Pompidou European Hospital, Assistance Publique des H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris Cit\u00e9 , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9602-5162","authenticated-orcid":false,"given":"Romain","family":"Cohen","sequence":"additional","affiliation":[{"name":"Sorbonne University, Department of Medical Oncology, H\u00f4pital Saint-Antoine, AP-HP, and INSERM UMRS 938, \u00c9quipe Instabilit\u00e9 des Microsatellites et Cancer, \u00c9quipe Labellis\u00e9e par la Ligue Nationale Contre le Cancer, SIRIC CURAMUS, Centre de recherche Saint Antoine , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lonardi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology 1, Istituto Oncologico Veneto Istituto di Ricovero e Cura a Carattere Scientifico , Padua,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1304-8340","authenticated-orcid":false,"given":"Ben","family":"Boursi","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sheba Medical Center, Tel-Hashomer , Tel-Aviv, ; , Tel-Aviv,","place":["Israel Israel"]},{"name":"Tel-Aviv University , Tel-Aviv, ; , Tel-Aviv,","place":["Israel 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Rome,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8137-5415","authenticated-orcid":false,"given":"Javier","family":"Ros","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Vall d\u2019Hebron University Hospital, Vall d\u2019Hebron Barcelona Hospital Campus , Barcelona,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Sabella","sequence":"additional","affiliation":[{"name":"First Division of Pathology, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Rossi","sequence":"additional","affiliation":[{"name":"First Division of Pathology, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , 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Pisa,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5377-135X","authenticated-orcid":false,"given":"Michael J","family":"Overman","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5103-7095","authenticated-orcid":false,"given":"Thierry","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Sorbonne University, Department of Medical Oncology, H\u00f4pital Saint-Antoine, AP-HP, and INSERM UMRS 938, \u00c9quipe Instabilit\u00e9 des Microsatellites et Cancer, \u00c9quipe Labellis\u00e9e par la Ligue Nationale Contre le Cancer, SIRIC CURAMUS, Centre de recherche Saint Antoine , 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