Research Papers:

CD80-CD28 signaling controls the progression of inflammatory colorectal carcinogenesis

Marco Scarpa _, Paola Brun, Melania Scarpa, Susan Morgan, Andrea Porzionato, Andromachi Kotsafti, Marina Bortolami, Andrea Buda, Renata D’Incà, Veronica Macchi, Giacomo C. Sturniolo, Massimo Rugge, Romeo Bardini, Ignazio Castagliuolo, Imerio Angriman and Carlo Castoro

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Oncotarget. 2015; 6:20058-20069. https://doi.org/10.18632/oncotarget.2780

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Marco Scarpa1,*, Paola Brun2,*, Melania Scarpa1, Susan Morgan3, Andrea Porzionato2, Andromachi Kotsafti1, Marina Bortolami4, Andrea Buda4, Renata D’Incà4, Veronica Macchi2, Giacomo C. Sturniolo4, Massimo Rugge5, Romeo Bardini4, Ignazio Castagliuolo2, Imerio Angriman4,§, Carlo Castoro1,§

1Oncological Surgery Unit, Veneto Institute of Oncology IOV – IRCCS, Padova 35128, Italy

2Department of Molecular Medicine, University of Padova, Padova 35128, Italy

3Department of Histopathology, Sheffield Teaching Hospitals, Sheffield S10 2JF, UK

4Department of Surgery Oncology and Gastroenterology, University of Padova, Padova 35128, Italy

5Department of Medicine, University of Padova, Padova 35128, Italy

*These authors have contributed equally to this work

§These senior authors contributed equally to this work

Correspondence to:

Marco Scarpa, e-mail: [email protected]

Keywords: ulcerative colitis, colorectal carcinogenesis, antigen presenting cells, CD8+ T cells, intestinal epithelial cells

Received: September 18, 2014     Accepted: November 19, 2014     Published: January 19, 2015


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.

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