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

S Derks, X Liao, AM Chiaravalli, X Xu, MC Camargo… - Oncotarget, 2016 - ncbi.nlm.nih.gov
S Derks, X Liao, AM Chiaravalli, X Xu, MC Camargo, E Solcia, F Sessa, T Fleitas…
Oncotarget, 2016ncbi.nlm.nih.gov
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 …
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.
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