PD-L1 Expression Promotes Epithelial to Mesenchymal Transition in Human Esophageal Cancer

• Published in: Cellular physiology and biochemistry Vol. 42; no. 6; pp. 2267 - 2280
• Main Authors: Chen, Lujun, Xiong, Yuqi, Li, Jing, Zheng, Xiao, Zhou, Qi, Turner, Abbey, Wu, Changping, Lu, Binfeng, Jiang, Jingting
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01-01-2017; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Ablation; Aged; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Cadherins - genetics; Cadherins - metabolism; Cancer therapies; Cell growth; Cell Line, Tumor; Cell Movement; Cell Survival; Colorectal cancer; Epithelial to mesenchymal transition; Epithelial-Mesenchymal Transition; Esophageal cancer; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Female; Gastric cancer; Genotype & phenotype; Humans; Immunoglobulins; Immunohistochemistry; Ligands; Lymphocytes; Male; Medical prognosis; Metastasis; Middle Aged; Original Paper; PD-L1; Phenotype; Prognosis; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; Recombinant Proteins - biosynthesis; Recombinant Proteins - isolation & purification; Recombinant Proteins - pharmacology; RNA, Small Interfering - metabolism; Signal Transduction - drug effects; Stem cells; Survival analysis; Vimentin - genetics; Vimentin - metabolism; United States > US; China; Epithelial to mesenchymal transition; PD-L1; Esophageal cancer
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000480000

Background/Aims: PD-L1 (Programmed cell death 1 ligand 1, PD-L1), an essential immune checkpoint molecule in the tumor microenvironment, is an important target for cancer immunotherapy. We have previously reported that its expression in human gastric and esophageal cancer tissues is significantly associated with cancer progression and patients’ postoperative prognoses. Its expression in cancer cells is well known to inhibit the T cell-mediated anti-tumor response, and this mechanism of action has been targeted for cancer immunotherapy. As of now, the autonomous effect of PD-L1 on cancer cells is not well understood, thus our present study aimed to examine the role of PD-L1 intervention in cellular biological functions, especially epithelial to mesenchymal transition (EMT), of the human esophageal cancer cell line, Eca-109 cells. Methods: Immunohistochemistry assay was used to investigate the correlation between expression of PD-L1 and EMT markers in human esophageal cancer tissues. Intervention of PD-L1 by using RNAi and over-expression methods were used to study the role of PD-L1 in regulation of biological behaviors and EMT in Eca-109 cells. Results: Our clinical and pathological data demonstrated that tumor samples in the EMT positive subgroup had higher PD-L1 expression than those in the EMT negative subgroup. By manipulating PD-L1 expression in Eca-109 cells either through ablation or overexpression of wild type and the cytoplasmic domain-truncated mutant, we demonstrated that PD-L1 expression significantly promoted the cell viability, migration and EMT phenotype. Furthermore, our study also indicated that PD-1 fusion protein mediated stimulation of PD-L1 and the cytoplasmic domain of PD-L1 played a critical role in promoting EMT phenotype of Eca-109 cells, thereby suggesting that PD-1 receptor usually by triggering the reverse signaling can effect PD-L1 mediated regulation of esophageal cancer cell response. Conclusion: Our present study reveals a tumor cell-autonomous role of PD-L1 signaling in promoting EMT in human esophageal cancer.