title: CD80-CD28 signaling controls the progression of inflammatory colorectal carcinogenesis.
abstract: In patients with ulcerative colitis (UC) the cumulative risk of colon cancer is lower than the actual rate of dysplasia suggesting an efficient immune surveillance mechanism. Since the co-stimulatory molecule CD80 is overexpressed in dysplastic colonic mucosa of UC patients and T-cell activation entails effective costimulation, we aimed to evaluate the functional implication of CD80 signaling in colonic UC-associated carcinogenesis. In humans, we observed that the percentage of CD80+ and HLA-A+ IEC was increased in the dysplastic colonic mucosa of UC patients. In vitro, IEC activated CD8+ T-cells through a CD80-dependent pathway. Finally, in the AOM/DSS-induced colonic adenocarcinoma model CD80 signaling inhibition significantly increased the frequency and extension of high-grade dysplasia, whereas enhancing CD80 activity with an anti-CTLA4 antibody significantly decreased colonic dysplasia. In conclusion, CD80 signaling between IEC and T-cells represents a key factor controlling the progression from low to high grade dysplasia in inflammatory colonic carcinogenesis.
authors.affiliation: Oncological Surgery Unit, Veneto Institute of Oncology IOV - IRCCS, Padova 35128, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Scarpa
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova 35128, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Brun
authors.affiliation: Oncological Surgery Unit, Veneto Institute of Oncology IOV - IRCCS, Padova 35128, Italy.
authors.forename: Melania
authors.initials: M
authors.lastname: Scarpa
authors.affiliation: Department of Histopathology, Sheffield Teaching Hospitals, Sheffield S10 2JF, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Morgan
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova 35128, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Porzionato
authors.affiliation: Oncological Surgery Unit, Veneto Institute of Oncology IOV - IRCCS, Padova 35128, Italy.
authors.forename: Andromachi
authors.initials: A
authors.lastname: Kotsafti
authors.affiliation: Department of Surgery Oncology and Gastroenterology, University of Padova, Padova 35128, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Bortolami
authors.affiliation: Department of Surgery Oncology and Gastroenterology, University of Padova, Padova 35128, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Buda
authors.affiliation: Department of Surgery Oncology and Gastroenterology, University of Padova, Padova 35128, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: D'Incà
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova 35128, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Macchi
authors.affiliation: Department of Surgery Oncology and Gastroenterology, University of Padova, Padova 35128, Italy.
authors.forename: Giacomo C
authors.initials: GC
authors.lastname: Sturniolo
authors.affiliation: Department of Medicine, University of Padova, Padova 35128, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.affiliation: Department of Surgery Oncology and Gastroenterology, University of Padova, Padova 35128, Italy.
authors.forename: Romeo
authors.initials: R
authors.lastname: Bardini
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova 35128, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Castagliuolo
authors.affiliation: Department of Surgery Oncology and Gastroenterology, University of Padova, Padova 35128, Italy.
authors.forename: Imerio
authors.initials: I
authors.lastname: Angriman
authors.affiliation: Oncological Surgery Unit, Veneto Institute of Oncology IOV - IRCCS, Padova 35128, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Castoro
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D018122:B7-1 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D018106:CD28 Antigens
keywords: CD8+ T cells; antigen presenting cells; colorectal carcinogenesis; intestinal epithelial cells; ulcerative colitis