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Prognostic value of PD-L1 and PD-1 expression in pulmonary neuroendocrine tumors

Authors Fan Y, Ma K, Wang C, Ning J, Hu Y, Dong D, Dong X, Geng Q, Li E, Wu Y

Received 15 June 2016

Accepted for publication 31 August 2016

Published 6 October 2016 Volume 2016:9 Pages 6075—6082

DOI https://doi.org/10.2147/OTT.S115054

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ru Chen

Peer reviewer comments 3

Editor who approved publication: Dr Ingrid Espinoza


Yangwei Fan,1,* Ke Ma,1,* Chuying Wang,1 Jing Ning,1 Yuan Hu,1 Danfeng Dong,1 Xuyuan Dong,1 Qianqian Geng,2 Enxiao Li,1 Yinying Wu1

1Department of Medical Oncology, 2Department of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China

*These authors contributed equally to this work

Purpose: Programmed death 1 (PD-1) receptor and its ligand, programmed death ligand-1 (PD-L1), play critical roles in the immune invasion of various tumors. This study aimed to explore the clinical significance of PD-L1/PD-1 expression in the progression of pulmonary neuroendocrine tumors (PNETs).
Methods:
The expression of PD-L1 and PD-1 in 80 patients diagnosed with PNETs were investigated. Immunohistochemical analysis was performed on 80 formalin-fixed paraffin-embedded tissue specimens from PNETs and 20 corresponding cancer-adjacent tissue specimens.
Results:
Tissues from PNETs had higher levels of PD-L1 (58.8%) and PD-1 (51.3%) compared to the cancer-adjacent tissues (25% and 20%, respectively). Meanwhile, PD-L1 expression was associated with PD-1 expression (P=0.007). PD-L1 expression was significantly associated with histological type (P=0.014) and tumor stage (P=0.014). Univariate analyses showed that the overall survival time of PNETs patients was significantly associated with PD-L1 expression in cancer cells (P=0.003), PD-1 expression in tumor-infiltrating lymphocytes (P=0.001), tumor node metastasis stage (P<0.05), and distant metastasis (P<0.001). Additionally, multivariate analysis revealed that PD-L1 expression, PD1 expression, and distant metastasis of PNETs were independently associated with survival time. Moreover, Kaplan–Meier survival curves analysis revealed that patients with negative PD-L1 and PD-1 expression had better prognoses.
Conclusion:
Data suggested that PD-L1 and PD-1 can be useful prognostic biomarkers for survival and can pave the way toward new immunotherapy regimens against PNETs through targeting the PD-L1/PD-1 pathway.

Keywords:
pulmonary neuroendocrine tumors, PD-L1, PD-1, prognosis

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