Dual role of CD73 as a signaling molecule and adenosine-generating enzyme in colorectal cancer progression and immune evasion

Lian, Weidong; Jiang, Dan; Lin, Wandie; Jiang, Muhong; Zhang, Yujie; Wang, Hui; Zhao, Liang

doi:10.7150/ijbs.87440

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Theranostics

International Journal of Medical Sciences

Nanotheranostics

Journal of Cancer

Journal of Genomics

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Int J Biol Sci 2024; 20(1):137-151. doi:10.7150/ijbs.87440 This issue Cite

Research Paper

Dual role of CD73 as a signaling molecule and adenosine-generating enzyme in colorectal cancer progression and immune evasion

Weidong Lian^1,2*, Dan Jiang^3*, Wandie Lin^1,3, Muhong Jiang^1,3, Yujie Zhang^1,3, Hui Wang^4✉, Liang Zhao^1,3✉

1. Department of Pathology, Nanfang Hospital, Southern Medical University Guangzhou, China.
2. The National Key Clinical Specialty, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University Guangzhou, China.
3. Department of Pathology & Guangdong Province Key Laboratory of Molecular Tumor Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
4. Department of Medical Oncology, Affiliated Tumour Hospital of Guangzhou Medical University, Guangzhou, China.
* These authors contributed equally to this work.

Citation:

Lian W, Jiang D, Lin W, Jiang M, Zhang Y, Wang H, Zhao L. Dual role of CD73 as a signaling molecule and adenosine-generating enzyme in colorectal cancer progression and immune evasion. Int J Biol Sci 2024; 20(1):137-151. doi:10.7150/ijbs.87440. https://www.ijbs.com/v20p0137.htm

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Abstract

Metastasis and limited benefits of immune checkpoint blockade are two obstacles to the battle against colorectal cancer (CRC). CD73, encoded by the gene 5'-Nucleotidase Ecto (NT5E), is a major enzyme that generates extracellular adenosine. However, whether CD73 affects cancer progression and immune response in CRC remains unclear. Here, the clinical significance of CD73 was assessed in human CRC specimens using immunohistochemistry and bioinformatic analyses. We demonstrated that CD73 is elevated in CRC tissues, particularly in those with metastasis, and correlates with poor prognosis. Gain- and loss-of-function experiments demonstrate that tumor CD73 supports tumor progression and impairs the viability and effector functions of CD8⁺ T cells. Targeting CD73 on CRC cells reduces their malignant phenotypes and improves the anti-cancer response of CD8⁺ T cells in the tumor microenvironment (TME). Moreover, the combination of CD73 blockade and PD-1 inhibitors exhibited enhanced anti-cancer effects when compared to a single-agent treatment. Thus, CD73 may be a promising target in the treatment of CRC.

Keywords: colorectal cancer, CD73, tumor progression, tumor immune, immune checkpoint blockade

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APA

Lian, W., Jiang, D., Lin, W., Jiang, M., Zhang, Y., Wang, H., Zhao, L. (2024). Dual role of CD73 as a signaling molecule and adenosine-generating enzyme in colorectal cancer progression and immune evasion. International Journal of Biological Sciences, 20(1), 137-151. https://doi.org/10.7150/ijbs.87440.

ACS

Lian, W.; Jiang, D.; Lin, W.; Jiang, M.; Zhang, Y.; Wang, H.; Zhao, L. Dual role of CD73 as a signaling molecule and adenosine-generating enzyme in colorectal cancer progression and immune evasion. Int. J. Biol. Sci. 2024, 20 (1), 137-151. DOI: 10.7150/ijbs.87440.

NLM

CSE

Lian W, Jiang D, Lin W, Jiang M, Zhang Y, Wang H, Zhao L. 2024. Dual role of CD73 as a signaling molecule and adenosine-generating enzyme in colorectal cancer progression and immune evasion. Int J Biol Sci. 20(1):137-151.

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