A PD-L2-based immune marker signature helps to predict survival in resected pancreatic ductal adenocarcinoma

Autor: Yiyin Zhang, Jin Xu, Jie Hua, Jiang Liu, Chen Liang, Qingcai Meng, Miaoyan Wei, Bo Zhang, Xianjun Yu, Si Shi
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-13 (2019)
Druh dokumentu: article
ISSN: 2051-1426
DOI: 10.1186/s40425-019-0703-0
Popis: Abstract Background Programmed cell death protein 1 (PD-1) is a key immune checkpoint that regulates peripheral tolerance and protects against autoimmunity. Programmed death ligand-2 (PD-L2) is a less studied ligand to PD-1 and has yet to be fully explored, especially in pancreatic ductal adenocarcinoma (PDAC). Methods In this study, we performed immunohistochemistry to detect the PD-L2, CD3, CD8, transforming growth factor-β2 (TGF-β2) and FOXP3 levels in paraffin sections from 305 patients with resected PDAC as a training set. Expression levels of intratumoral and stromal immune markers were compared in relation to survival using Kaplan-Meier curves, random survival forest model and survival tree analysis. A multivariable Cox proportional-hazards model of associated markers was used to calculate the risk scores. Results PD-L2 was expressed in 71.5% of PDAC samples and showed strong correlations with CD3+, CD8+ T cells and FOXP3+ regulatory T cell densities. High levels of intratumoral PD-L2 and FOXP3 were related to poor survival; only stromal FOXP3 overexpression was associated with worse prognosis. Four patterns generated from survival tree analysis demonstrated that PD-L2low stromalFOXP3low patients had the longest survival, while PD-L2high intratumoralCD3low patients had the shortest survival (P
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