Cordycepin Enhances the Anticancer Efficacy of PD-L1 Blockade by Modulating the Tumor Microenvironment of Colon Cancer

Chen Feng; Rongzhang Chen; Xinran Gao; Weiwei Fang; Shaoxian Wu; Lujun Chen; Xiao Zheng; Xinyue Ji; Maoling Yuan; Yuanyuan Fu; Hanjie Ying; Tao Shen; Dawei Zhu; Jingting Jiang

doi:10.1016/j.ejphar.2024.177089

Cordycepin Enhances the Anticancer Efficacy of PD-L1 Blockade by Modulating the Tumor Microenvironment of Colon Cancer

Eur J Pharmacol. 2024 Nov 1:177089. doi: 10.1016/j.ejphar.2024.177089. Online ahead of print.

Authors

Chen Feng¹, Rongzhang Chen², Xinran Gao³, Weiwei Fang⁴, Shaoxian Wu⁵, Lujun Chen⁶, Xiao Zheng⁷, Xinyue Ji⁸, Maoling Yuan⁹, Yuanyuan Fu¹⁰, Hanjie Ying¹¹, Tao Shen¹², Dawei Zhu¹³, Jingting Jiang¹⁴

Affiliations

¹ Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China. Electronic address: [email protected].
² Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China. Electronic address: [email protected].
³ Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China. Electronic address: [email protected].
⁴ Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China. Electronic address: [email protected].
⁵ Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China. Electronic address: [email protected].
⁶ Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China. Electronic address: [email protected].
⁷ Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China. Electronic address: [email protected].
⁸ Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China. Electronic address: [email protected].
⁹ Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China. Electronic address: [email protected].
¹⁰ Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Department of Gynecology, Changzhou Traditional Chinese Medicine Hospital, Changzhou, Jiangsu, 213003, China. Electronic address: [email protected].
¹¹ College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, Jiangsu, 211816, China; Soochow University, Suzhou, Jiangsu, 215031, China. Electronic address: [email protected].
¹² College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, Jiangsu, 211816, China. Electronic address: [email protected].
¹³ Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China. Electronic address: [email protected].
¹⁴ Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China. Electronic address: [email protected].

PMID: 39489279
DOI: 10.1016/j.ejphar.2024.177089

Abstract

Background: PD-L1 blockade has been found to be effective in treating multiple malignancies. Combined therapy is proposed to provide better therapeutic effects. Cordycepin, a prominent bioactive compound found in cordyceps, can inhibit the development of various cancers.

Purpose: This study aimed to determine the efficacy of combined anti-PD-L1 antibody and cordycepin in tumor treatment.

Methods: A single-cell RNA sequencing was used to analyze the mechanism of combined treatment.

Results: Combination therapy of anti-PD-L1 and cordycepin significantly inhibited tumor growth by regulating the T cell ratio and improving the function of CD8⁺T cells. Furthermore, cordycepin promoted the reprogramming of type-II macrophages into type-I macrophages, a process confirmed through flow cytometry analysis of the underlying mechanism.

Conclusion: Our findings demonstrate that the combination of anti-PD-L1 and cordycepin effectively suppressed tumor growth by regulating the proportion of T cells and reprograming type-II macrophages.

Keywords: Cordycepin; Macrophage; Tissue-resident memory T cells; Tumor microenvironment; anti-PD-L1.