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

Med Sci Monit. 2016 Oct 27:22:4017-4025. doi: 10.12659/msm.900661.

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.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • B7-H1 Antigen / biosynthesis*
  • Biomarkers, Tumor / biosynthesis
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • ErbB Receptors / metabolism
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Male
  • Mice
  • Retrospective Studies
  • Transplantation, Heterologous / methods*

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • ErbB Receptors