CD73 Promotes Tumor Progression in Patients with Esophageal Squamous Cell Carcinoma
1
Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
2
Department of Nursing, Meiho University, Pingtung 912, Taiwan
3
School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
4
Department of Thoracic & Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Seiichiro Abe
Cancers 2021, 13(16), 3982; https://doi.org/10.3390/cancers13163982
Received: 6 July 2021
/
Revised: 5 August 2021
/
Accepted: 5 August 2021
/
Published: 9 August 2021
(This article belongs to the Special Issue Advanced Squamous Cell Carcinoma)
Simple Summary
The immune system plays important roles in antitumor activities. However, increasing evidence shows that tumor cells develop several mechanisms to escape the immune attack, resulting in immunosuppression. One of the most important immunosuppressive pathways is the CD73-adenosinergic pathway. In addition, this pathway participates in the development of cancer, including tumor cell proliferation, angiogenesis, and anti-inflammation mechanisms. Moreover, CD73 can mediate the invasion and metastasis of tumor cells via the regulation of cell interactions with the extracellular matrix components. Therefore, overcoming immunosuppression to restore the antitumor functions of T cells may be explored as a potential treatment strategy. Overexpression of CD73 promotes the malignant properties of cancers and is associated with specific clinical characteristics and worse prognosis in many types of cancers. The current study is the first to investigate the role of CD73 in determining the clinical outcomes of patients with esophageal squamous cell carcinoma.
Cluster of differentiation (CD)-73 plays pivotal roles in the regulation of immune reactions via the production of extracellular adenosine, and the overexpression of CD73 is associated with worse outcomes in several types of cancers. Here, we identified 167 esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy, including 64 and 103 patients with high and low expression levels of CD73, respectively. Univariate and multivariate analyses showed high expression of CD73 was an independent prognostic factor for worse disease-free survival and overall survival. In addition, we selected another cohort consisting of 38 ESCC patients receiving nivolumab or pembrolizumab and found that treatment response and survival benefit to immunotherapy were strongly correlated with the expression levels of CD73/programmed death ligand 1. Moreover, the transwell assay revealed knockdown of CD73 in two ESCC cell lines, TE1 and KYSE30, exhibited significantly reduced abilities of cell invasion and migration. CD73 silencing also showed that the protein expression levels of CD73, vimentin, and snail were downregulated, while those of E-cadherin were upregulated in Western blotting. The findings of our study indicate CD73 may be an independent prognostic factor for ESCC patients who underwent esophagectomy. Furthermore, it may be associated with the patient responses to immunotherapy.
View Full-Text
Keywords:
esophageal cancer; CD73; squamous cell carcinoma; epithelial–mesenchymal transition; esophagectomy
▼
Show Figures
Figure 1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
- Supplementary File 1:
ZIP-Document (ZIP, 340 KiB)
MDPI and ACS Style
Chen, Y.-H.; Lu, H.-I.; Lo, C.-M.; Li, S.-H. CD73 Promotes Tumor Progression in Patients with Esophageal Squamous Cell Carcinoma. Cancers 2021, 13, 3982. https://doi.org/10.3390/cancers13163982
AMA Style
Chen Y-H, Lu H-I, Lo C-M, Li S-H. CD73 Promotes Tumor Progression in Patients with Esophageal Squamous Cell Carcinoma. Cancers. 2021; 13(16):3982. https://doi.org/10.3390/cancers13163982
Chicago/Turabian StyleChen, Yen-Hao, Hung-I Lu, Chien-Ming Lo, and Shau-Hsuan Li. 2021. "CD73 Promotes Tumor Progression in Patients with Esophageal Squamous Cell Carcinoma" Cancers 13, no. 16: 3982. https://doi.org/10.3390/cancers13163982
Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
