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P064. Mucosal immune environment in colonic carcinogenesis: CD80 expression on epithelial cell peaked in dysplasia and its inhibition decreased inflammation but did not stop carcinogenesis progression


M. Scarpa1, P. Brun2, I. Castagliuolo2, L. Nai3, M. Scarpa3, A. Porzionato3, A. Buda2, R. D'Incà2, G.C. Sturniolo4, R. Bardini2, C. Castoro5, I. Angriman6

1University of Padua, Dip Scienze Chirurgiche e Gastroenterologiche Clinica Chirurgica I, Padua, Italy; 2University of Padua, Padua, Italy; 3University of Padua, Padova, Italy; 4University of Padua, Dip. Di Scienze Chirurgiche e Gastroenterologiche, Padua, Italy; 5Venetian Oncology Institute, Padua, Italy; 6University of Padua, Gastrointestinal and Surgical Sciences, Padua, Italy



Background: The presence of an immunosurveillance against cancerogenesis in UC was recently observed. The aims of this study were to verify this hypothesis exploring the interplay between epithelium and CD8 T cell in human colonic carcinogenesis and evaluating the effect of CD80 signalling inhibition.

Methods: Twenty nine patients diagnosed with UC, UC with dysplasia, colonic adenoma, or colonic cancer were recruited at the moment of colonic resection. Mucosal samples were obtained during the colectomy and included specimens from healthy, dysplastic and neoplastic colon. Single cell suspensions were obtained by enzymatic digestion of mucosal specimens and subjected to Fluorescence-Activated Cell Sorting (FACS) to determine the proportion of epithelial cells (Cytokeratine 20, Cyt-20+) acting as antigen presenting cells (expressing CD80, CD40, HLA I or HLA II) and the proportion of CD8+ T cells activated (positive for CD28, CD38 or CD69). The second part of the study involved a mouse model of inflammation-related colon carcinogenesis with azoxymethane (AOM) and dextran sodium sulfate-induced (DSS). After the injection of AOM mice received 3 or 5 cycles of 3% DSS in their drinking water, each cycle consisted of 5 days of treatment followed by 14 days of rest. Animals were randomized to receive monoclonal anti-CD80 antibodies (10 µg/mouse) or isotype control, and sacrificed after 28 days.

Results: The proportion of Cyt-20+ CD80+ and Cyt-20+ HLA II+ cells was higher in dysplasia than in non dysplastic colonic tissue (p = 0.03 and p = 0.07, respectively). The proportion of Cyt-20+ CD80+ and Cyt-20+ CD40+ cells was higher in dysplasia than in invasive adenocarcinoma (p = 0.07 and p = 0.04, respectively). The proportion of CD8+ T cell expressing CD28 and CD38 was higher in dysplastic mucosa than in the mucosa with no neoplastic changes (p = 0.01 and p = 0.01, respectively). In mice that received anti-CD80 antibodies after AOM and 3 cycles of DSS dysplasia extension was significantly higher than in mice that received a control antibody (p = 0.04).

Conclusions: The proportion of epithelial cells acting as antigen presenting cells peaks in the dysplastic colonic mucosa at the same point of activated CD8+ T cells. CD80 inhibition increased dysplasia extension as opposed to common anti-inflammatory therapies such as 5ASA. These data confirm the hypothesis that an active immunosurveillance mechanism is implicated in controlling the progression from dysplasia to neoplasia.