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27 October 2016 : Animal Research  

Induction of Patient-Derived Xenograft Formation and Clinical Significance of Programmed Cell Death Ligand 1 (PD-L1) in Lung Cancer Patients

Yuanyuan MaBCDEF, Panpan ZhangBCDEF, Guo AnBD, Xiaolong ZhangBD, Liyi ZhangCF, Jiahui SiDF, Jianzhi ZhangD, Yue YangACEG

DOI: 10.12659/MSM.900661

Med Sci Monit 2016; 22:4017-4025

Abstract

BACKGROUND: The immune checkpoint of programmed cell death ligand 1 (PD-L1) commonly expressed in solid cancers, and the blockade of this molecule show promising results in advanced cancers, including lung cancer. The relevance of PD-L1 to patient-derived xenograft (PDX) formation and clinicopathological characteristics in early stage lung cancer have not been fully elucidated.

MATERIAL AND METHODS: Cell counting kit-8 and flow cytometry were carried out to examine proliferation and apoptosis in PC9 and H520 cells transfected with siRNAs. Nod-scid mice were used to establish PDX. Immunohistochemistry was done to investigate PD-L1 expression in tumor tissues.

RESULTS: PD-L1 was detected in lung cancer cell lines and 45.45% of primary tumor tissues from a cohort of 209 lung cancer patients. Cell growth was restrained and apoptosis was induced when PD-L1 was inhibited in PC9 and H520 cells. In addition, we successfully established 16 PDX models from tissues from 43 cases of primary lung cancer. Higher PD-L1 expression rates (75%) was observed in primary tumors with PDX formation compared to protein expression rate (44.44%) in tumors without PDX formation. Consistently, a 1.9-fold increase of PDX formation frequency was identified in the PD-L1 positive tumors than in the PD-L1 negative tumors. Moreover, PD-L1 was found to be related to smoking, histological type, and pathological stage. Importantly, PD-L1 overexpression was associated with shorter overall survival (OS) of lung cancer patients.

CONCLUSIONS: This study suggests that overexpression of PD-L1 could induce PDX formation and is related to poor outcome for the lung cancer patients.

Keywords: Antigens, CD274

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750