Research Papers:

Immunoclassification characterized by CD8 and PD-L1 expression is associated with the clinical outcome of gastric cancer patients

Weili Wang _, Kuansong Wang, Zihua Chen, Ling Chen, Wei Guo, Ping Liao, Daniel Rotroff, Todd C. Knepper, Zhaoqian Liu, Wei Zhang, Howard L. Mcleod and Yijing He

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Oncotarget. 2018; 9:12164-12173. https://doi.org/10.18632/oncotarget.24037

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Weili Wang1, Kuansong Wang2, Zihua Chen3, Ling Chen3, Wei Guo2, Ping Liao1, Daniel Rotroff5, Todd C. Knepper4, Zhaoqian Liu1, Wei Zhang1, Howard L. Mcleod1,4 and Yijing He1,4

1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan, China

2Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China

3Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China

4Moffitt Cancer Center, DeBartolo Family Personalized Medicine Institute, Tampa, FL, USA

5Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA

Correspondence to:

Yijing He, email: [email protected]

Howard L. Mcleod, email: [email protected]

Keywords: gastric cancer; immunoclassification; chemotherapy; Epstein-Barr virus (EBV)

Received: July 22, 2017     Accepted: November 15, 2017     Published: January 06, 2018


Background: Gastric cancer (GC) is a major cause of cancer deaths, especially in Eastern Asia. Current classification systems, including the WHO, Lauren, and TCGA, have clarified the pathological and molecular profiles of GC. However, these classifications lack an association with clinical outcome and guidance for medication selection.

Objective: We aimed to identify a new immunoclassification for GC to better predict patient prognosis and aid in patient selection for immunotherapy.

Results: For all samples, 35 were EBV positive (+) and 112 were EBV negative (-). EBV infection was associated with the number of CD3+ T cells (OR = 2.91 95% CI 1.27-6.68, p = 0.012) and PD-L1 expression in TME (OR = 2.57, 95% CI 1.13–5.82, p = 0.024). EBV+ patients showed a poor overall survival (OS) compared with EBV- patients (HR = 2.37; 95% CI, 1.03–5.41; p = 0.011). Importantly, WIR patients lived significantly shorter than SIR patients with high CD8+ T cells and low PD-L1 expression (HR = 3.37; 95% CI, 1.63–6.97; p = 0.015).

Materials and Methods: 147 formalin-fixed and paraffin-embedded (FFPE) samples of GC were obtained. Epstein-Barr virus (EBV) infection was measured. Immune markers including CD3, CD8 and PD-L1 were detected by immunohistochemistry (IHC) at tumor infiltration area (TI) and invasive margin area (IM) in tumor microenvironment (TME). PD-L1 expression was assessed by immunoreactive score (IRS) system. For immunoclassification, patients were classified into two subgroups: strong immunoreaction (SIR) and weak immunoreaction (WIR) defined by the number of CD8+ T cells and PD-L1 expression in TI.

Conclusions: In this study, we suggest a new immunoclassification for gastric cancer which is associated with patient outcome and may provide a way to guide immunotherapy in the future.

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