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Cell Physiol Biochem. 2017;42(6):2267-2280. doi: 10.1159/000480000. Epub 2017 Aug 17.

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

Chen L1,2,3,4, Xiong Y1,2,3, Li J1,2,3, Zheng X1,2,3, Zhou Q1,2,3, Turner A4, Wu C1,2,3, Lu B4, Jiang J1,2,3.

Author information

1
Department of Tumor Biological Treatment, Changzhou, China.
2
Jiangsu Engineering Research Center for Tumor Immunotherapy and, Changzhou, China.
3
Institute of Cell Therapy, the Third Affiliated Hospital of Soochow University, Changzhou, China.
4
Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Abstract

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.

KEYWORDS:

Epithelial to mesenchymal transition; Esophageal cancer; PD-L1

PMID:
28848143
DOI:
10.1159/000480000
[Indexed for MEDLINE]
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