Next Article in Journal
Role of Gene Therapy in Pancreatic Cancer—A Review
Next Article in Special Issue
Interplay of Viral Infection, Host Cell Factors and Tumor Microenvironment in the Pathogenesis of Nasopharyngeal Carcinoma
Previous Article in Journal
Epigenetic Modifications as Biomarkers of Tumor Development, Therapy Response, and Recurrence across the Cancer Care Continuum
Previous Article in Special Issue
The Immunomodulatory Capacity of an Epstein-Barr Virus Abortive Lytic Cycle: Potential Contribution to Viral Tumorigenesis
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle
Cancers 2018, 10(4), 102;

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

Department of Pathology, Ospedale di Circolo, 21100 Varese, Italy
Department of Surgical and Medical Sciences, University of Insubria, 21100 Varese, Italy
Department of Molecular Medicine, University of Pavia and IRCCS S. Matteo Hospital, Pavia 27100, Italy
Author to whom correspondence should be addressed.
Received: 28 February 2018 / Revised: 26 March 2018 / Accepted: 29 March 2018 / Published: 1 April 2018
(This article belongs to the Special Issue Epstein–Barr Virus Associated Cancers)
PDF [1317 KB, uploaded 3 May 2018]


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. View Full-Text
Keywords: gastric cancer; PD-L1; EBV; MSI; tumor infiltrating lymphocytes gastric cancer; PD-L1; EBV; MSI; tumor infiltrating lymphocytes

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

De Rosa, S.; Sahnane, N.; Tibiletti, M.G.; Magnoli, F.; Vanoli, A.; Sessa, F.; Chiaravalli, A.M. EBV+ and MSI Gastric Cancers Harbor High PD-L1/PD-1 Expression and High CD8+ Intratumoral Lymphocytes. Cancers 2018, 10, 102.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top