Clinicopathologic implications of immune classification by PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in stage II and III gastric cancer patients
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Jiwon Koh1, Chan-Young Ock2, Jin Won Kim3, Soo Kyung Nam4, Yoonjin Kwak4, Sumi Yun5, Sang-Hoon Ahn6, Do Joong Park6, Hyung-Ho Kim6, Woo Ho Kim1, Hye Seung Lee4
1Department of Pathology, Seoul National University College of Medicine, Jongno-gu, Seoul 03080, Republic of Korea
2Department of Internal Medicine, Seoul National University Hospital, Jongno-gu, Seoul 03080, Republic of Korea
3Department of Internal Medicine, Seoul National University Bundang Hospital, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, Republic of Korea
4Department of Pathology, Seoul National University Bundang Hospital, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, Republic of Korea
5Department of Pathology, Soonchunhyang University Seoul Hospital, Yongsan-gu, Seoul 04401, Republic of Korea
6Department of Surgery, Seoul National University Bundang Hospital, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, Republic of Korea
Hye Seung Lee, email: email@example.com
Keywords: gastric cancer, programmed cell death 1 ligand 1, tumor-infiltrating lymphocytes, cancer microenvironment
Received: November 22, 2016 Accepted: February 06, 2017 Published: February 17, 2017
We co-assessed PD-L1 expression and CD8+ tumor-infiltrating lymphocytes in gastric cancer (GC), and categorized into 4 microenvironment immune types. Immunohistochemistry (PD-L1, CD8, Foxp3, E-cadherin, and p53), PD-L1 mRNA in situ hybridization (ISH), microsatellite instability (MSI), and EBV ISH were performed in 392 stage II/III GCs treated with curative surgery and fluoropyrimidine-based adjuvant chemotherapy, and two public genome databases were analyzed for validation. PD-L1+ was found in 98/392 GCs (25.0%). The proportions of immune types are as follows: PD-L1+/CD8High, 22.7%; PD-L1−/CD8Low, 22.7%; PD-L1+/CD8Low, 2.3%; PD-L1−/CD8High, 52.3%. PD-L1+/CD8High type accounted for majority of EBV+ and MSI-high (MSI-H) GCs (92.0% and 66.7%, respectively), and genome analysis from public datasets demonstrated similar pattern. PD-L1−/CD8High showed the best overall survival (OS) and PD-L1−/CD8Low the worst (P < 0.001). PD-L1 expression alone was not associated with OS, however, PD-L1−/CD8High type compared to PD-L1+/CD8High was independent favorable prognostic factor of OS by multivariate analysis (P = 0.042). Adaptation of recent molecular classification based on EBV, MSI, E-cadherin, and p53 showed no significant survival differences. These findings support the close relationship between PD-L1/CD8 status based immune types and EBV+, MSI-H GCs, and their prognostic significance in stage II/III GCs.
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