Induction of Patient-Derived Xenograft Formation and Clinical Significance of Programmed Cell Death Ligand 1 (PD-L1) in Lung Cancer Patients
Yuanyuan Ma, Panpan Zhang, Guo An, Xiaolong Zhang, Liyi Zhang, Jiahui Si, Jianzhi Zhang, Yue Yang
Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China (mainland)
Med Sci Monit 2016; 22:4017-4025
Available online: 2016-10-27
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, Lung Neoplasms