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 journalArticle

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-y 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)32925-32932
Number of pages8
JournalOncotarget
Volume7
Issue number22
DOIs
Publication statusPublished - May 31 2016

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Keywords

  • EBV-infected gastric cancers
  • MSI gastric cancer
  • PD-1 inhibitors
  • PD-L1

ASJC Scopus subject areas

  • Oncology

Cite this

Derks, S., Liao, X., Chiaravalli, A. M., Xu, X., Camargo, M. C., Solcia, E., Sessa, F., Fleitas, T., Freeman, G. J., Rodig, S. J., Rabkin, C. S., & Bass, A. J. (2016). Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers. Oncotarget, 7(22), 32925-32932. https://doi.org/10.18632/oncotarget.9076