EBV⁺ and MSI Gastric Cancers Harbor High PD-L1/PD-1 Expression and High CD8⁺ Intratumoral Lymphocytes

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 immunohistochemi...

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Published in:Cancers Vol. 10; no. 4; p. 102
Main Authors: De Rosa, Simona, Sahnane, Nora, Tibiletti, Maria Grazia, Magnoli, Francesca, Vanoli, Alessandro, Sessa, Fausto, Chiaravalli, Anna Maria
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 01-04-2018
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Summary: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; < 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 ( < 0.001). Despite being associated with a better prognosis both in the whole series ( < 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.
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ISSN:2072-6694
2072-6694
DOI:10.3390/cancers10040102