EBV+ and MSI gastric cancers harbor high PD-L1/PD-1 expression and high CD8+ intratumoral lymphocytes

Simona de Rosa, Nora Sahnane, Maria Grazia Tibiletti, Francesca Magnoli, Alessandro Vanoli, Fausto Sessa, Anna Maria Chiaravalli

Research output: Contribution to journalArticlepeer-review

Abstract

Both EBV+ and MSI gastric cancers (GCs) have high lymphoid infiltration which is rare in MSS/EBV cancers. PD-L1/PD-1 interaction leads to a down-regulated immune response and it is one of the most promising targets for gastric cancer immunotherapy. PD-L1/PD-1 and CD8 expression were immunohistochemically investigated in a series of 169 FFPE GCs, including 33 EBV+, 59 MSI and 77 MSS/EBV cases. PD-L1 membrane immunoreactivity in more than 5% of tumor cells was present in 31/169 GCs and was associated with high levels of CD8 intraepithelial lymphocytes (TILs; p < 0.001). PD-L1+ cases were mainly poorly differentiated (71%), intestinal type (85%) and high lymphoid response (HLR; 90%) tumors. PD-L1 expression was only present in EBV+ (46%), MSI (24%) and rare MSS/EBV (3%) GCs with high CD8+ TILs (p < 0.001). Despite being associated with a better prognosis both in the whole series (p < 0.05) and in the MSI subset, PD-L1 is not an independent prognostic factor. PD-L1 gene amplification was detected in 3/17 cases, including 2/7 EBV+ and 1/8 MSI GC. PD-1+ TILs were significantly higher in EBV+ than MSI and MSS/EBV cases. PD-L1/PD-1 pathway is selectively activated in HLR GCs and could be considered an emerging therapeutic target, particularly for EBV and MSI GCs.

Original languageEnglish
Article number102
JournalCancers
Volume10
Issue number4
DOIs
Publication statusPublished - Apr 1 2018

Keywords

  • EBV
  • Gastric cancer
  • MSI
  • PD-L1
  • Tumor infiltrating lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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