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, Carlo Castoro

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)20058-20069
Number of pages12
JournalOncotarget
Volume6
Issue number24
Publication statusPublished - 2015

Keywords

  • Antigen presenting cells
  • CD8+ T cells
  • Colorectal carcinogenesis
  • Intestinal epithelial cells
  • Ulcerative colitis

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'CD80-CD28 signaling controls the progression of inflammatory colorectal carcinogenesis'. Together they form a unique fingerprint.

Cite this