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

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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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Human Herpesvirus 4
Stomach Neoplasms
Microsatellite Instability
Neoplasms
Atlases
Gene Expression Profiling
Interferons
Immunohistochemistry
Clinical Trials
Genome
Staining and Labeling
Ligands
Therapeutics
Genes

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., ... 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

Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers. / Derks, Sarah; Liao, Xiaoyun; Chiaravalli, Anna M.; Xu, Xinsen; Camargo, M. Constanza; Solcia, Enrico; Sessa, Fausto; Fleitas, Tania; Freeman, Gordon J.; Rodig, Scott J.; Rabkin, Charles S.; Bass, Adam J.

In: Oncotarget, Vol. 7, No. 22, 31.05.2016, p. 32925-32932.

Research output: Contribution to journalArticle

Derks, S, Liao, X, Chiaravalli, AM, Xu, X, Camargo, MC, Solcia, E, Sessa, F, Fleitas, T, Freeman, GJ, Rodig, SJ, Rabkin, CS & Bass, AJ 2016, 'Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers', Oncotarget, vol. 7, no. 22, pp. 32925-32932. https://doi.org/10.18632/oncotarget.9076
Derks S, Liao X, Chiaravalli AM, Xu X, Camargo MC, Solcia E et al. Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers. Oncotarget. 2016 May 31;7(22):32925-32932. https://doi.org/10.18632/oncotarget.9076
Derks, Sarah ; Liao, Xiaoyun ; Chiaravalli, Anna M. ; Xu, Xinsen ; Camargo, M. Constanza ; Solcia, Enrico ; Sessa, Fausto ; Fleitas, Tania ; Freeman, Gordon J. ; Rodig, Scott J. ; Rabkin, Charles S. ; Bass, Adam J. / Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers. In: Oncotarget. 2016 ; Vol. 7, No. 22. pp. 32925-32932.
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