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

Le Ying, Feng Yan, Qiaohong Meng, Liang Yu, Xiangliang Yuan, Michael P. Gantier, Bryan R.G. Williams, David W. Chan, Liyun Shi, Yugang Tu, Peihua Ni, Xuefeng Wang, Weisan Chen, Xingxing Zang, Dakang Xu, Yiqun Hu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalOncoImmunology
DOIs
StateAccepted/In press - Feb 16 2018

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Stomach Neoplasms
Biomarkers
Survival
Tumor Escape
T-Lymphocytes
Immune Evasion
Neoplasms
Regulatory T-Lymphocytes
Immunotherapy
Cluster Analysis
Immunity
Cell Count
Immunohistochemistry

Keywords

  • Clustering analysis
  • gastric cancer
  • multiplexed immunohistochemistry
  • prognostic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

PD-L1 expression is a prognostic factor in subgroups of gastric cancer patients stratified according to their levels of CD8 and FOXP3 immune markers. / Ying, Le; Yan, Feng; Meng, Qiaohong; Yu, Liang; Yuan, Xiangliang; Gantier, Michael P.; Williams, Bryan R.G.; Chan, David W.; Shi, Liyun; Tu, Yugang; Ni, Peihua; Wang, Xuefeng; Chen, Weisan; Zang, Xingxing; Xu, Dakang; Hu, Yiqun.

In: OncoImmunology, 16.02.2018.

Research output: Contribution to journalArticle

Ying, L, Yan, F, Meng, Q, Yu, L, Yuan, X, Gantier, MP, Williams, BRG, Chan, DW, Shi, L, Tu, Y, Ni, P, Wang, X, Chen, W, Zang, X, Xu, D & Hu, Y 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', OncoImmunology. https://doi.org/10.1080/2162402X.2018.1433520
Ying, Le ; Yan, Feng ; Meng, Qiaohong ; Yu, Liang ; Yuan, Xiangliang ; Gantier, Michael P. ; Williams, Bryan R.G. ; Chan, David W. ; Shi, Liyun ; Tu, Yugang ; Ni, Peihua ; Wang, Xuefeng ; Chen, Weisan ; Zang, Xingxing ; Xu, Dakang ; Hu, Yiqun. / PD-L1 expression is a prognostic factor in subgroups of gastric cancer patients stratified according to their levels of CD8 and FOXP3 immune markers. In: OncoImmunology. 2018.
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AU - Yu, Liang

AU - Yuan, Xiangliang

AU - Gantier, Michael P.

AU - Williams, Bryan R.G.

AU - Chan, David W.

AU - Shi, Liyun

AU - Tu, Yugang

AU - Ni, Peihua

AU - Wang, Xuefeng

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AU - Zang, Xingxing

AU - Xu, Dakang

AU - Hu, Yiqun

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AB - 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.

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