Oncotarget

Research Papers:

CD8+/FOXP3+ ratio and PD-L1 expression associated with survival in pT3N0M0 stage esophageal squamous cell cancer

Yingming Zhu, Minghuan Li, Dianbin Mu, Li Kong, Jianbo Zhang, Fen Zhao, Zhenxiang Li, Xuemei Liu, Cong Bo and Jinming Yu _

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Oncotarget. 2016; 7:71455-71465. https://doi.org/10.18632/oncotarget.12213

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Abstract

Yingming Zhu1, Minghuan Li1, Dianbin Mu2, Li Kong1, Jianbo Zhang2, Fen Zhao1, Zhenxiang Li1, Xuemei Liu1, Cong Bo1, Jinming Yu1

1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, China

2Department of Pathology, Shandong Cancer Hospital and Institute, Shandong University Jinan, China

Correspondence to:

Jinming Yu, email: sdyujinming@sina.cn

Minghuan Li, email: lminghuan@sina.com

Keywords: esophageal squamous cell cancer, CD8, forkhead box protein 3, programmed death receptor ligand-1, pT3N0M0

Received: May 28, 2016     Accepted: September 16, 2016     Published: September 23, 2016

ABSTRACT

Data describing relationships between the tumor immune microenvironment and patient outcome are limited for esophageal squamous cell cancer (ESCC). The present study investigated the prognostic values of programmed death-ligand 1 (PD-L1) expression and CD8+ or forkhead box protein 3+ (FOXP3+) tumor-infiltrating lymphocytes (TILs) in 133 pathological T3N0M0 stage ESCC patients who underwent radical resection without neoadjuvant or adjuvant therapy. CD8+ and FOXP3+ TIL densities as well as PD-L1 levels in tumor cells and lymphocytes, were assessed through immunohistochemical staining. Patient survival was not associated with CD8+ or FOXP3+ TILs alone, but PD-L1 expression and the CD8+/FOXP3+ ratio were independent predictors of both disease-free and overall survival. PD-L1 expression correlated with age (p = 0.029), tumor length (p < 0.001), tumor differentiation status (p = 0.002) and reduced intratumoral CD8+ TIL density (p < 0.001). Our results suggest pT3N0M0 ESCC clinical outcomes correlate with CD8+ and FOXP3+ TIL densities and PD-L1 levels. Moreover, an intrinsic mechanism for induction of PD-L1 overexpression may be occurring during early tumor oncogenesis. This information may be useful for stratifying patients and guide the application of checkpoint blockade therapy in ESCC.


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