Esophageal adenocarcinoma (EAC) is an increasingly common disease with a dismal 5-year survival of 10-15%. In the first systematic evaluation of the PD-1 pathway in EAC, we identify expression of PD-L2 in cancer cells in 51.7% of EACs. Epithelial PD-L1 was expressed on only 2% of cases, though PD-L1 positive immune cells were observed in 18% of EACs. We also evaluated expression in the precursor lesion of EAC, Barrett's Esophagus (BE), which emerges following gastric reflux-induced esophageal inflammation, and found PD-L2 expression in BE but not in non-BE esophagitis. As the progression from squamous esophagitis to BE is accompanied by a transition from a Th1 to Th2 immune response, we hypothesized that the Th2 cytokines IL-4/IL-13 could contribute to PD-L2 induction. We confirmed these cytokines can augment PD-L2 expression in EAC cell lines. These results suggest that the inflammatory environment in BE and EAC may contribute to the expression of PD-L2. Furthermore, the potential for PD-1 receptor blockade to be effective in EACs with epithelial PD-L2 or immune cell PD-L1 expression should be evaluated in clinical trials.
- Received February 11, 2015.
- Revision received June 11, 2015.
- Accepted June 11, 2015.
- Copyright © 2015, American Association for Cancer Research.