{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T11:58:42Z","timestamp":1777636722370,"version":"3.51.4"},"reference-count":38,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-007274"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007274"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/MED-PAT\/32462\/2017"],"award-info":[{"award-number":["PTDC\/MED-PAT\/32462\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background. The tumor immune microenvironment exerts a pivotal influence in tumor initiation and progression. The aim of this study was to analyze the immune context of sporadic and familial adenomatous polyposis (FAP) lesions along the colorectal adenoma\u2013carcinoma sequence (ACS). Methods. We analyzed immune cell counts (CD3+, CD4+, CD8+, Foxp3+, and CD57+), tumor mutation burden (TMB), MHC-I expression and PD-L1 expression of 59 FAP and 74 sporadic colorectal lesions, encompassing adenomas with low-grade dysplasia (LGD) (30 FAP; 30 sporadic), adenomas with high-grade dysplasia (22 FAP; 30 sporadic), and invasive adenocarcinomas (7 FAP; 14 sporadic). Results. The sporadic colorectal ACS was characterized by (1) a stepwise decrease in immune cell counts, (2) an increase in TMB and MHC-I expression, and (3) a lower PD-L1 expression. In FAP lesions, we observed the same patterns, except for an increase in TMB along the ACS. FAP LGD lesions harbored lower Foxp3+ T cell counts than sporadic LGD lesions. A decrease in PD-L1 expression occurred earlier in FAP lesions compared to sporadic ones. Conclusions. The colorectal ACS is characterized by a progressive loss of adaptive immune infiltrate and by the establishment of a progressively immune cold microenvironment. These changes do not appear to be related with the loss of immunogenicity of tumor cells, or to the onset of an immunosuppressive tumor microenvironment.<\/jats:p>","DOI":"10.3390\/ijms22189791","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T10:31:34Z","timestamp":1631269894000},"page":"9791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Adaptive Immune Landscape of the Colorectal Adenoma\u2013Carcinoma Sequence"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5860-8313","authenticated-orcid":false,"given":"Jo\u00e3o Augusto","family":"Freitas","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3377-0530","authenticated-orcid":false,"given":"Irene","family":"Gullo","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Department of Pathology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o (CHUSJ), 4200-319 Porto, Portugal"},{"name":"Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"}]},{"given":"Diogo","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"}]},{"given":"Sara","family":"Miranda","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"}]},{"given":"Louisa","family":"Spaans","sequence":"additional","affiliation":[{"name":"Faculty of Health, Medicine and Life Sciences-Maastricht University, 6229 ER Maastricht, The Netherlands"}]},{"given":"L\u00eddia","family":"Pinho","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0823-4891","authenticated-orcid":false,"given":"Joana","family":"Reis","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8049-2890","authenticated-orcid":false,"given":"Fabiana","family":"Sousa","sequence":"additional","affiliation":[{"name":"High Risk Consultation of Digestive Tumors, Department of General Surgery, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o (CHUSJ), 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4306-769X","authenticated-orcid":false,"given":"Manuela","family":"Baptista","sequence":"additional","affiliation":[{"name":"High Risk Consultation of Digestive Tumors, Department of General Surgery, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o (CHUSJ), 4200-319 Porto, Portugal"}]},{"given":"Carlos","family":"Resende","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"}]},{"given":"Dina","family":"Leit\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9282-0708","authenticated-orcid":false,"given":"Cec\u00edlia","family":"Dur\u00e3es","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7132-4094","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1964-1006","authenticated-orcid":false,"given":"F\u00e1tima","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Department of Pathology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o (CHUSJ), 4200-319 Porto, Portugal"},{"name":"Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4741-8415","authenticated-orcid":false,"given":"Jos\u00e9 Carlos","family":"Machado","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/0092-8674(90)90186-I","article-title":"A genetic model for colorectal tumorigenesis","volume":"61","author":"Fearon","year":"1990","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/359235a0","article-title":"APC mutations occur early during colorectal 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