Dendritic Cells in Barrett’s Esophagus and Esophageal Adenocarcinoma

Abstract

Background Like other premalignant conditions that develop in the presence of chronic inflammation, the development and progression of Barrett's esophagus is associated with the development of an immune response, but how this immune response is regulated is poorly understood. A comprehensive literature search failed to find any report of the presence of dendritic cells in Barrett's intestinal metaplasia and esophageal adenocarcinoma and this prompted our study. Material and Methods We used immunohistochemical staining and electron microscopy to examine whether dendritic cells are present in Barrett's esophagus and esophageal adenocarcinoma. Immunohistochemical staining with CD83, a specific marker for dendritic cells, was performed on paraffin-embedded sections of Barrett's intestinal metaplasia (IM, n=12), dysplasia (n=11) and adenocarcinoma (n=14). Results CD83+ cells were identified in the lamina propria surrounding intestinal type glands in Barrett's IM, dysplasia, and cancer tissues. Computerized quantitative analysis showed that the numbers of dendritic cells were significantly higher in cancer tissues. Double immunostaining with CD83, CD20, and CD3, and electron microscopy demonstrated that dendritic cells are present in Barrett's esophagus and form clusters with T cells and B cells directly within the lamina propria. Conclusions These findings demonstrate that dendritic cells are present in Barrett's tissues, with a significant increase in density in adenocarcinoma compared to benign Barrett's esophagus. Dendritic cells may have a role in the pathogenesis and immunotherapy treatment of Barrett's esophagus and adenocarcinoma.

Dendritic Cell-Associated Immune Inflammation of Cardiac Mucosa: A Possible Factor in the Formation of Barrett’s Esophagus

“…14,27 In brief, after visualization of CD83 with the ABC substrate kit, sections were washed with 0.1 M glycine-hydrochloric acid buffer, pH 2.2, and then incubated with anti-CD3 or anti-CD20 antibody. After rinsing in TPBS, the sections were incubated with biotinylated secondary antibody and then with alkaline phosphataseconjugated streptavidin (Dako) or with ABC (Dako).…”

“…The electron microscopic identification of dendritic cells was carried out according to their distinctive ultrastructural features which include the tubulovesicular system and atypical granules as previously used. 14,28 Figure 2 Direct contacts between dendritic cells and lymphocytes in cardiac mucosa (a-g). CD83 antigen was visualized using ABC immunoperoxidase reaction (brown reaction product) (a-g) while The use of dendritic cell-specific markers, including CD83 and DC-SIGN, demonstrated the presence of dendritic cells in all tissue specimens where they represented a minor cell population (Fig.…”

“…[9][10][11] A variety of inflammatory and immune cells populate the Barrett's esophagus mucosa, including T and B lymphocytes, mast cells, and macrophages. [12][13][14] We recently reported that antigen-presenting dendritic cells are present in Barrett's esophagus with a significant increase in their spatial density in adenocarcinoma compared to benign Barrett's esophagus. 14 Dendritic cells are powerful initiators and regulators of immune reactions [15][16][17][18][19] and thus may have a role in the pathogenesis of Barrett's esophagus and adenocarcinoma.…”

“…[12][13][14] We recently reported that antigen-presenting dendritic cells are present in Barrett's esophagus with a significant increase in their spatial density in adenocarcinoma compared to benign Barrett's esophagus. 14 Dendritic cells are powerful initiators and regulators of immune reactions [15][16][17][18][19] and thus may have a role in the pathogenesis of Barrett's esophagus and adenocarcinoma. 14 In contrast to Barrett's esophagus, cardiac mucosa has received only very limited attention, possibly because it is not associated with an increased risk of cancer.…”

“…14 Dendritic cells are powerful initiators and regulators of immune reactions [15][16][17][18][19] and thus may have a role in the pathogenesis of Barrett's esophagus and adenocarcinoma. 14 In contrast to Barrett's esophagus, cardiac mucosa has received only very limited attention, possibly because it is not associated with an increased risk of cancer.…”