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Oncoimmunology. 2018 Feb 20;7(6):e1433520. doi: 10.1080/2162402X.2018.1433520. eCollection 2018.

PD-L1 expression is a prognostic factor in subgroups of gastric cancer patients stratified according to their levels of CD8 and FOXP3 immune markers.

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Faculty of Medical Laboratory Science, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China.
Institute of Ageing Research, Hangzhou Normal University School of Medicine, Hangzhou, P. R. China.
Department of Tea Science, Zhejiang University, Hangzhou, P. R. China.
Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, P. R. China.
Hudson Institute of Medical Research, Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia.
Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P. R. China.
Department of Microbiology and Immunology, Nanjing University of Chinese Medicine, Nanjing, P. R. China.
Cell Signaling Technology, Inc., Asia Pacific.
La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, Australia.
Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY; Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.


Current studies aiming at identifying single immune markers with prognostic value have limitations in the context of complex antitumor immunity and cancer immune evasion. Here, we show how the integration of several immune markers influences the predictions of prognosis of gastric cancer (GC) patients. We analyzed Tissue Microarray (TMA) by multiplex immunohistochemistry and measured the expression of immune checkpoint molecule PD-L1 together with antitumor CD8 T cells and immune suppressive FOXP3 Treg cells in a cohort of GC patients. Unsupervised hierarchical clustering analysis of these markers was used to define correlations between CD8 T, FOXP3 Treg and PD-L1 cell densities. We found that FOXP3 and PD-L1 densities were elevated while CD8 T cells were decreased in tumor tissues compared to their adjacent normal tissues. However, patient stratification based on each one of these markers individually did not show significant prognostic value on patient survival. Conversely, combination of the ratios of CD8/FOXP3 and CD8/PD-L1 enabled the identification of patient subgroups with different survival outcomes. As such, high densities of PD-L1 in patients with high CD8/FOXP3 and low CD8/PD-L1 ratios correlated with increased survival. Collectively, this work demonstrates the need for the integration of several immune markers to obtain more meaningful survival prognosis and patient stratification. In addition, our work provides insights into the complex tumor immune evasion and immune regulation by the tumor-infiltrating effector and suppressor cells, informing on the best use of immunotherapy options for treating patients.


Clustering analysis; gastric cancer; multiplexed immunohistochemistry; prognostic

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