Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers

Sarah Derks, Xiaoyun Liao, Anna M Chiaravalli, Xinsen Xu, M Constanza Camargo, Enrico Solcia, Fausto Sessa, Tania Fleitas, Gordon J Freeman, Scott J Rodig, Charles S Rabkin, Adam J Bass

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Gastric cancer (GC) is a deadly disease with limited treatment options. Recent studies with PD-1 inhibition have shown promising results in GC, but key questions remain regarding which GC subclass may respond best. In other cancers, expression of the PD-1 ligand PD-L1 has been shown to identify cancers with greater likelihood of response to PD-1 blockade. We here show with immunohistochemistry that Epstein-Barr Virus (EBV)+ GCs (n = 32) have robust PD-L1 expression not seen in other GCs. In EBV+ GC, we observed PD-L1 staining in tumor cells in 50% (16/32) and immune cells in 94% (30/32) of cases. Among EBV-negative GCs, PD-L1 expression within tumors cells was observed only in cases with microsatellite instability (MSI), although 35% of EBV-/MSS GCs possessed PD-L1 expression of inflammatory cells. Moreover, distinct classes of GC showed different patterns of PD-L1+ immune cell infiltrations. In both EBV+ and MSI tumors, PD-L1+ inflammatory cells were observed to infiltrate the tumor. By contrast, such cells remained at the tumor border of EBV-/MSS GCs. Consistent with these findings, we utilized gene expression profiling of GCs from The Cancer Genome Atlas study to demonstrate that an interferon-γ driven gene signature, an additional proposed marker of sensitivity to PD-1 therapy, were enriched in EBV+ and MSI GC. These data suggest that patients with EBV+ and MSI GC may have greater likelihood of response to PD-1 blockade and that EBV and MSI status should be evaluated as variables in clinical trials of these emerging inhibitors.

Original languageEnglish
Pages (from-to)32925-32
Number of pages8
JournalOncotarget
Volume7
Issue number22
DOIs
Publication statusPublished - 2016

Cite this

Derks, S., Liao, X., Chiaravalli, A. M., Xu, X., Camargo, M. C., Solcia, E., ... Bass, A. J. (2016). Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers. Oncotarget, 7(22), 32925-32. https://doi.org/10.18632/oncotarget.9076