{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:47:17Z","timestamp":1777355237941,"version":"3.51.4"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T00:00:00Z","timestamp":1592524800000},"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":["NORTE-01-0145-FEDER-000003\/000029"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000003\/000029"]}],"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"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/BIM-MEC\/2834\/2014"],"award-info":[{"award-number":["PTDC\/BIM-MEC\/2834\/2014"]}],"id":[{"id":"10.13039\/501100001871","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":["PAC-PRECISE-LISBOA-01-0145-FEDER-016394,"],"award-info":[{"award-number":["PAC-PRECISE-LISBOA-01-0145-FEDER-016394,"]}],"id":[{"id":"10.13039\/501100001871","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":["UID\/BIM\/50005\/2019"],"award-info":[{"award-number":["UID\/BIM\/50005\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Gastric carcinoma (GC) represents the most common cause of death in patients with common variable immunodeficiency (CVID). However, a limited number of cases have been characterised so far. In this study, we analysed the clinical features, bacterial\/viral infections, detailed morphology and immune microenvironment of nine CVID patients with GC. The study of the immune microenvironment included automated digital counts of CD20+, CD4+, CD8+, FOXP3+, GATA3+ and CD138+ immune cells, as well as the evaluation of PD-L1 expression. Twenty-one GCs from non-CVID patients were used as a control group. GC in CVID patients was diagnosed mostly at early-stage (n = 6\/9; 66.7%) and at younger age (median-age: 43y), when compared to non-CVID patients (p &lt; 0.001). GC pathogenesis was closely related to Helicobacter pylori infection (n = 8\/9; 88.9%), but not to Epstein-Barr virus (0.0%) or cytomegalovirus infection (0.0%). Non-neoplastic mucosa (non-NM) in CVID-patients displayed prominent lymphocytic gastritis (100%) and a dysfunctional immune microenvironment, characterised by higher rates of CD4+\/CD8+\/Foxp3+\/GATA3+\/PD-L1+ immune cells and the expected paucity of CD20+ B-lymphocytes and CD138+ plasma cells, when compared to non-CVID patients (p &lt; 0.05). Changes in the immune microenvironment between non-NM and GC were not equivalent in CVID and non-CVID patients, reflecting the relevance of immune dysfunction for gastric carcinogenesis and GC progression in the CVID population.<\/jats:p>","DOI":"10.3390\/cells9061498","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T10:43:58Z","timestamp":1592563438000},"page":"1498","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Dysfunctional Immune System in Common Variable Immunodeficiency Increases the Susceptibility to Gastric Cancer"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3377-0530","authenticated-orcid":false,"given":"Irene","family":"Gullo","sequence":"first","affiliation":[{"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"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Catarina","family":"Costa","sequence":"additional","affiliation":[{"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":"Susana L.","family":"Silva","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Centro de Imunodefici\u00eancias Prim\u00e1rias do Centro Acad\u00e9mico de Medicina de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1600-190 Lisbon, Portugal"}]},{"given":"Cristina","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Centro de Imunodefici\u00eancias Prim\u00e1rias do Centro Acad\u00e9mico de Medicina de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1600-190 Lisbon, Portugal"}]},{"given":"Adriana","family":"Motta","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Centro de Imunodefici\u00eancias Prim\u00e1rias do Centro Acad\u00e9mico de Medicina de Lisboa, 1649-028 Lisbon, Portugal"}]},{"given":"Sara P.","family":"Silva","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Centro de Imunodefici\u00eancias Prim\u00e1rias do Centro Acad\u00e9mico de Medicina de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1600-190 Lisbon, Portugal"}]},{"given":"R\u00faben Duarte","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Centro de Imunodefici\u00eancias Prim\u00e1rias do Centro Acad\u00e9mico de Medicina de Lisboa, 1649-028 Lisbon, Portugal"}]},{"given":"Pedro","family":"Rosmaninho","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Centro de Imunodefici\u00eancias Prim\u00e1rias do Centro Acad\u00e9mico de Medicina de Lisboa, 1649-028 Lisbon, Portugal"}]},{"given":"Em\u00edlia","family":"Faria","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Imunoalergologia, Centro Hospitalar Hospitalar e Universit\u00e1rio de Coimbra, 3004-561 Coimbra, Portugal"}]},{"given":"Jos\u00e9 Torres da","family":"Costa","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Imunoalergologia, Centro Hospitalar Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o (CHUSJ), 4200-319 Porto, Portugal"}]},{"given":"Rita","family":"C\u00e2mara","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Imunoalergologia, Hospital Dr N\u00e9lio Mendon\u00e7a, 9000-177 Funchal, Portugal"}]},{"given":"Gilza","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Department of Pathology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o (CHUSJ), 4200-319 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0614-0576","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Santos-Antunes","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o (CHUSJ), 4200-319 Porto, Portugal"}]},{"given":"Carla","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Jos\u00e9 C.","family":"Machado","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1964-1006","authenticated-orcid":false,"given":"F\u00e1tima","family":"Carneiro","sequence":"additional","affiliation":[{"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"},{"name":"Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Ana E.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"},{"name":"Centro de Imunodefici\u00eancias Prim\u00e1rias do Centro Acad\u00e9mico de Medicina de Lisboa, 1649-028 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s10875-020-00758-x","article-title":"Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification","volume":"40","author":"Bousfiha","year":"2020","journal-title":"J. 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