Immune determinants of Barrett’s progression to esophageal adenocarcinoma

• DOI: 10.1172/jci.insight.143888
• Publication Date: 2020-12-08T19:00:42Z
• Authors: Kiran H. Lagisetty; Dyke P. McEwen; Derek J. Nancarrow; Johnathon G. Schi...; Daysha Ferrer-Torres; Dipankar Ray; Timothy L. Frankel; Jules Lin; Andrew C. Chang; Laura A. Kresty; David G. Beer
• Keywords: Esophageal adenocarcinoma; Barrett's esophagus

Esophageal adenocarcinoma (EAC) develops from Barrett's esophagus (BE), a chronic inflammatory state that can progress through series of transformative dysplastic states before tumor development. While molecular and genetic changes EAC tumors have been studied, immune microenvironment during progression to remain poorly understood. In this study, we identify potential immunologic occur BE-to-EAC progression. RNA sequencing (RNA-Seq) analysis on tissue samples patients undergoing surgical resection demonstrated subset chemokines cytokines, most notably IL6 CXCL8, increased BE EAC. xCell deconvolution investigating cell population the largest in expression occurred M2 macrophages, pro-B cells, eosinophils. Multiplex immunohistochemical staining microarrays showed populations high-grade dysplasia. contrast, sections were relatively poor, with rise PD-L1 loss CD8+ T cells. These data demonstrate is characterized by poor cytotoxic effector infiltration inhibitory signaling. findings suggest an immunosuppressive microenvironment, highlighting need for further studies explore modulatory therapy