{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:47:00Z","timestamp":1792093620387,"version":"4.4.0"},"reference-count":102,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["PI21\/00869"],"award-info":[{"award-number":["PI21\/00869"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["FORT23\/00006"],"award-info":[{"award-number":["FORT23\/00006"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Biobanking Infrastructure","award":["PT20\/00004"],"award-info":[{"award-number":["PT20\/00004"]}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica Hospital la Paz"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Interactions between colorectal tumours and their immune microenvironment critically influence disease progression and response to immunotherapy. However, most organoid systems fail to preserve the complex architecture and immune composition of the original tissue. Here, we applied the air\u2013liquid interface (ALI) organoid model to paired tumour and perilesional colon tissues from colorectal cancer patients to evaluate its ability to retain immune and genetic features and to reproduce responses to chemotherapy and immune checkpoint blockade. Methods: Fresh human tumour and matched healthy colon tissues were processed to generate ALI organoids. Their histological organization, immune cell composition (including CD45+ subsets), and genomic profiles were compared with those of the parental tissues and with conventional Matrigel organoids, either alone or co-cultured with peripheral blood mononuclear cells (PBMCs). Organoids were exposed to 5-FU and nivolumab (anti\u2013PD-1) to assess local immune modulation. Results: ALI organoids faithfully preserved the three-dimensional architecture, native immune infiltrates, and somatic mutational landscape of the source tissues. Importantly, upon PD-1 blockade with nivolumab, ALI organoids consistently exhibited a local expansion of regulatory T cells (Tregs), a phenomenon that could contribute to adaptive immune resistance. This response was not reproduced in PBMC\u2013Matrigel co-culture systems, highlighting the importance of preserving endogenous tumour\u2013immune interactions. Conclusions: Patient-derived ALI organoids represent a physiologically relevant platform that conserves key structural, immunological, and genomic hallmarks of colorectal cancer. By capturing clinically relevant immune remodeling events, such as Treg expansion following PD-1 blockade, this model provides a powerful tool for dissecting tumour\u2013immune interactions.<\/jats:p>","DOI":"10.3390\/cancers18010132","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T14:08:11Z","timestamp":1767190091000},"page":"132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Colorectal Air\u2013Liquid Interface Organoids Preserve Tumour-Immune Architecture and Reveal Local Treg Expansion After PD-1 Blockade"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5549-4093","authenticated-orcid":false,"given":"Laura","family":"C\u00f3rdoba","sequence":"first","affiliation":[{"name":"Biobank Platform, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7457-9583","authenticated-orcid":false,"given":"Francisco J.","family":"Cueto","sequence":"additional","affiliation":[{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Department of Medical Oncology, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n","family":"Cantero-Cid","sequence":"additional","affiliation":[{"name":"Digestive Surgery Service, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Digestive Surgery Department, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid, 28046 Madrid, Spain"},{"name":"Translational Research and Innovation in Surgery Group, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca","family":"Abad-Moret","sequence":"additional","affiliation":[{"name":"Digestive Surgery Service, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Digestive Surgery Service, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1922-7681","authenticated-orcid":false,"given":"Jaime","family":"\u00c1lvarez-Benayas","sequence":"additional","affiliation":[{"name":"ARIES Research Group, Universidad Antonio de Nebrija, 28248 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Fern\u00e1ndez-Felipe","sequence":"additional","affiliation":[{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Faculty of Health Sciences, Universidad UNIE, 28015 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Jim\u00e9nez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Biobank Platform, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Arvelo-Rosario","sequence":"additional","affiliation":[{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Mata-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Immunomodulation Laboratory, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Arranz-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Biobank Platform, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaiza","family":"Pedroche-Just","sequence":"additional","affiliation":[{"name":"Biobank Platform, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Nieto-Torrero","sequence":"additional","affiliation":[{"name":"Biobank Platform, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Valent\u00edn-Quiroga","sequence":"additional","affiliation":[{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Terr\u00f3n-Arcos","sequence":"additional","affiliation":[{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Fern\u00e1ndez-Pascual","sequence":"additional","affiliation":[{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Immunomodulation Laboratory, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"G\u00f3mez-Campelo","sequence":"additional","affiliation":[{"name":"Biobank Platform, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0717-3049","authenticated-orcid":false,"given":"Nieves","family":"Cubo-Mateo","sequence":"additional","affiliation":[{"name":"ARIES Research Group, Universidad Antonio de Nebrija, 28248 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Fern\u00e1ndez-Medina","sequence":"additional","affiliation":[{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Immunomodulation Laboratory, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hurtado-Navarro","sequence":"additional","affiliation":[{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Faculty of Health Sciences, Universidad UNIE, 28015 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"S\u00e1enz de Santa Mar\u00eda","sequence":"additional","affiliation":[{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"del Prado-Montero","sequence":"additional","affiliation":[{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agust\u00edn L.","family":"Santos","sequence":"additional","affiliation":[{"name":"Biobank Platform, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0093-9707","authenticated-orcid":false,"given":"Roberto","family":"Lozano-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Tumour Immunology Lab, IdiPAZ, La Paz University Hospital, 28046 Madrid, 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Spain"},{"name":"Biomedical Research Networking Center (CIBER), Respiratory Diseases (CibeRes), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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