CD80 expression promotes immune surveillance in Barrett's metaplasia

Melania Scarpa; Matteo Fassan; Andromachi Kotsafti; Stefano Realdon; Luigi Dall'Olmo; Tiziana Morbin; Francesco Cavallin; Luca Saadeh; Matteo Cagol; Rita Alfieri; Carlo Castoro; Massimo Rugge; Ignazio Castagliuolo; Marco Scarpa

doi:10.1080/2162402X.2019.1636618

CD80 expression promotes immune surveillance in Barrett's metaplasia

Oncoimmunology. 2019 Jul 23;8(10):e1636618. doi: 10.1080/2162402X.2019.1636618. eCollection 2019.

Authors

Affiliations

¹ Laboratory of Advanced Translational Research, Veneto Institute of Oncology IOV, IRCCS, Padua, Italy.
² Department of Medicine DIMED, University of Padua, Padua, Italy.
³ Accident and Emergency Unit, Hospital of Venice, Italy.
⁴ Independent Statistician, Solagna, Italy.
⁵ General Surgery Unit, University Hospital of Padova, Padova, Italy.
⁶ Department of Upper GI Surgery, Humanitas Research Hospital-Humanitas University, Rozzano, Italy.
⁷ Department of Molecular Medicine DMM, University of Padua, Padua, Italy.
⁸ General Surgery Unit, University Hospital of Padova, Italy.

Abstract

Esophageal adenocarcinoma (EAC) is the final step of a pathway starting with esophageal reflux disease, Barrett's metaplasia and Barrett's dysplasia. Positive costimulatory ligands such as CD80 have been suggested to contribute to anti-tumor T-cell efficacy. Here we report for the first time the role of CD80 in the inflammatory esophageal carcinogenesis and characterize the immune environment of EAC. Mucosa samples from cancer were obtained during esophagectomy from patients affected by EAC. Fresh biopsies were obtained from patients who underwent endoscopy for screening or follow-up. A rodent model of reflux induced esophageal carcinogenesis was created with an esophago-gastro-jejunostomy. CD80 expression was increased in epithelial cells during metaplasia in the inflammatory esophageal carcinogenesis cascade. Cd80 null mice as well as WT mice that received antiCD80 antibodies showed a higher rate of dysplasia and KI-67+ cells. These results suggest that CD80 mediates an active immune surveillance process in early inflammation-driven esophageal carcinogenesis.

Keywords: Barrett’s esophagus; CD80; adenocarcinoma; esophageal dysplasia; immune surveillance.

Publication types

Research Support, Non-U.S. Gov't

Grants and funding

This work was supported by the Current Research Funding from Italian Ministry of Health to Veneto Institute of Oncology IOV-IRCCS to Carlo Castoro and then to Marco Scarpa; Finalized Research Funds (awarded in 2011 to MICCE1 project) from the Veneto Region to Carlo Castoro.