CD80-CD28 Signaling Controls the Progression of Inflammatory Colorectal Carcinogenesis

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 Jan 18

PMID 25595911

Citations 18

Authors

Marco Scarpa

Paola Brun

Melania Scarpa

Susan Morgan

Andrea Porzionato

Andromachi Kotsafti

Marina Bortolami

Andrea Buda

Renata DInca

Veronica Macchi

Giacomo C Sturniolo

Massimo Rugge

Romeo Bardini

Ignazio Castagliuolo

Imerio Angriman

Carlo Castoro

Affiliations

Soon will be listed here.

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.

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