Int J Med Sci 2020; 17(7):939-945. doi:10.7150/ijms.42978 This issue

Research Paper

The extracts of Astragalus membranaceus overcome tumor immune tolerance by inhibition of tumor programmed cell death protein ligand-1 expression

Hsu-Liang Chang1, Yi-Hsuan Kuo2, Li-Hsien Wu2, Chih-Min Chang2,3, Kai-Jen Cheng2,4, Yu-Chang Tyan5, Che-Hsin Lee2,6,7,8,9✉

1. Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan
2. Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
3. Division of Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
4. Division of Nephrology, Department of Internal Medicine, Kaohsiung Municipal United Hospital, Kaohsiung 80457, Taiwan
5. Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung 80145, Taiwan
6. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
7. Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 804, Taiwan
8. Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
9. Aerosol Science Research Center, National Sun Yat-sen University, Kaohsiung, Taiwan, 80424, Taiwan

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Citation:
Chang HL, Kuo YH, Wu LH, Chang CM, Cheng KJ, Tyan YC, Lee CH. The extracts of Astragalus membranaceus overcome tumor immune tolerance by inhibition of tumor programmed cell death protein ligand-1 expression. Int J Med Sci 2020; 17(7):939-945. doi:10.7150/ijms.42978. Available from https://www.medsci.org/v17p0939.htm

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Abstract

A polysaccharide isolated from the radix of Astragalus membranaceus, called PG2, used in traditional Chinese medicine, with potential hematopoiesis inducing and immunomodulation activities. PG2 extracted from A. membranaceus has been demonstrated as a novel alternative medicine for cancer patients. Recently, we demonstrated that PG2 enhanced chemotherapy through bystander effect and reduced the expression of indoleamine 2, 3-dioxygenase 1 in tumor cells. Many tumors have been proven to have a high expression of programmed cell death protein ligand-1 (PD-L1), which binds with programmed cell death protein-1(PD-1) in immune cells, thus causing immune tolerance within the tumor microenvironment. With decreased expression of PD-L1, increased immune response can be observed, which might be helpful when developing tumor immunotherapy. The antitumor therapeutic effect mediated by PG2 may associate with an inflammatory immune response at the tumor site. However, the molecular mechanism that by which PG2 inhibits PD-L1 is still incompletely known. The expression of PD-L1 was decreased after tumor cells were treated with PG2. In addition, the cell signaling pathway in tumor cells was evaluated by Western blotting analysis after PG2 treatment. PG2 can downregulate the expression of PD-L1 on the cell surface via the protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase beta-1 (p70S6K) pathway. In conclusion, our results indicate that PG2 inhibits PD-L1 expression and plays a crucial role in immunotherapy, which might be a promising strategy combined with other treatments.

Keywords: the extracts of Astragalus membranaceus (PG2), programmed cell death protein ligand-1, tumor immune tolerance