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

摘要

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.