Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Int J Biol Sci 2024; 20(1):61-77. doi:10.7150/ijbs.83599 This issue Cite

Research Paper

Cancer Differentiation Inducer Chlorogenic Acid Suppresses PD-L1 Expression and Boosts Antitumor Immunity of PD-1 Antibody

Rui Li1#, Yun Zhan2#, Xiao Ding3, Jinjin Cui1, Yanxing Han2, Jinlan Zhang2, Jie Zhang4, Wenbin Li5, Lulu Wang1✉, Jiandong Jiang1,2✉

1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
2. State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
3. State Key Latoratory of Phytochemistry and Plant Resource in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, 650201, China.
4. Jiuzhang Biochemical Engineering Science and Technology Development Co., Ltd, Chengdu, Sichuan, 610041, China.
5. Department of Neuro-oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
# Equal contribution to the work.

✉ Corresponding author: Jiandong Jiang, 1 Tian Tan Xi Li, Beijing, China 100050; E-mail: jiang.jdongcom; Telephone: 86-10-6318 8423. Lulu Wang, 1 Tian Tan Xi Li, Beijing, China 100050; E-mail: wanglulucams.cn; Telephone: 86-10-6313 1808.

Citation:
Li R, Zhan Y, Ding X, Cui J, Han Y, Zhang J, Zhang J, Li W, Wang L, Jiang J. Cancer Differentiation Inducer Chlorogenic Acid Suppresses PD-L1 Expression and Boosts Antitumor Immunity of PD-1 Antibody. Int J Biol Sci 2024; 20(1):61-77. doi:10.7150/ijbs.83599. https://www.ijbs.com/v20p0061.htm
Other styles

File import instruction

Abstract

Graphic abstract

As immune checkpoint inhibitors have shown good clinical efficacy, immune checkpoint blockade has become a vital strategy in cancer therapy. However, approximately only 12.5% patients experience benefits from immunotherapy. Herein, we identified the cancer differentiation inducer chlorogenic acid (CGA, now in the phase II clinical trial in China for glioma treatment) to be a small-molecular immune checkpoint inhibitor that boosted the antitumor effects of the anti-PD-1 antibody. CGA suppressed the expression of PD-L1 induced by interferon-γ in tumor cell culture through inhibition of the p-STAT1-IRF1 pathway and enhanced activity of activated T-cells. In two murine tumor xenografts, combination therapy of CGA with anti-PD-1 antibody decreased the expression of PD-L1 and IRF1 and increased the inhibitory effect of the anti-PD-1 antibody on tumor growth. Particularly, the activity of tumor infiltrated T cells was enhanced by CGA. CGA improved the gene expression of granzymes in tumor-infiltrated immune cells. In conclusion, through induction of differentiation, CGA appeared to suppress the expression of PD-L1 on cancer cells, effectively promoting infiltrated T cells in the tumor and boosting the antitumor effect of the anti-PD-1 antibody. Thus, CGA might serve as a promising agent to enhance anticancer immunotherapy if combined with anti-PD-1 antibodies.

Keywords: Chlorogenic acid, Cancer differentiation inducer, PD-L1, Anti-PD-1 antibody, Combination therapy

Citation styles

APA
Li, R., Zhan, Y., Ding, X., Cui, J., Han, Y., Zhang, J., Zhang, J., Li, W., Wang, L., Jiang, J. (2024). Cancer Differentiation Inducer Chlorogenic Acid Suppresses PD-L1 Expression and Boosts Antitumor Immunity of PD-1 Antibody. International Journal of Biological Sciences, 20(1), 61-77. https://doi.org/10.7150/ijbs.83599.

ACS
Li, R.; Zhan, Y.; Ding, X.; Cui, J.; Han, Y.; Zhang, J.; Zhang, J.; Li, W.; Wang, L.; Jiang, J. Cancer Differentiation Inducer Chlorogenic Acid Suppresses PD-L1 Expression and Boosts Antitumor Immunity of PD-1 Antibody. Int. J. Biol. Sci. 2024, 20 (1), 61-77. DOI: 10.7150/ijbs.83599.

NLM
Li R, Zhan Y, Ding X, Cui J, Han Y, Zhang J, Zhang J, Li W, Wang L, Jiang J. Cancer Differentiation Inducer Chlorogenic Acid Suppresses PD-L1 Expression and Boosts Antitumor Immunity of PD-1 Antibody. Int J Biol Sci 2024; 20(1):61-77. doi:10.7150/ijbs.83599. https://www.ijbs.com/v20p0061.htm

CSE
Li R, Zhan Y, Ding X, Cui J, Han Y, Zhang J, Zhang J, Li W, Wang L, Jiang J. 2024. Cancer Differentiation Inducer Chlorogenic Acid Suppresses PD-L1 Expression and Boosts Antitumor Immunity of PD-1 Antibody. Int J Biol Sci. 20(1):61-77.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image

©2024 Ivyspring International Publisher. Terms of use