Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer

Chen Feng; Rongzhang Chen; Weiwei Fang; Xinran Gao; Hanjie Ying; Xiao Zheng; Lujun Chen; Jingting Jiang

doi:10.3389/fphar.2023.1144330

Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer

Front Pharmacol. 2023 Apr 17:14:1144330. doi: 10.3389/fphar.2023.1144330. eCollection 2023.

Authors

Chen Feng^{1

2

3}, Rongzhang Chen^{1

2

3}, Weiwei Fang^{1

2

3}, Xinran Gao^{1

2

3}, Hanjie Ying⁴, Xiao Zheng^{1

2

3}, Lujun Chen^{1

2

3}, Jingting Jiang^{1

2

3}

Affiliations

¹ Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Chang Zhou, Jiang Su, China.
² Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Chang Zhou, Jiang Su, China.
³ Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Chang Zhou, Jiang Su, China.
⁴ College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, Jiang Su, China.

Abstract

Cordycepin is widely considered a direct tumor-suppressive agent. However, few studies have investigated as the effect of cordycepin therapy on the tumor microenvironment (TME). In our present study, we demonstrated that cordycepin could weaken the function of M1-like macrophages in the TME and also contribute to macrophage polarization toward the M2 phenotype. Herein, we established a combined therapeutic strategy combining cordycepin and an anti-CD47 antibody. By using single-cell RNA sequencing (scRNA-seq), we showed that the combination treatment could significantly enhance the effect of cordycepin, which would reactivate macrophages and reverse macrophage polarization. In addition, the combination treatment could regulate the proportion of CD8⁺ T cells to prolong the progression-free survival (PFS) of patients with digestive tract malignancies. Finally, flow cytometry validated the changes in the proportions of tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs). Collectively, our findings suggested that the combination treatment of cordycepin and the anti-CD47 antibody could significantly enhance tumor suppression, increase the proportion of M1 macrophages, and decrease the proportion of M2 macrophages. In addition, the PFS in patients with digestive tract malignancies would be prolonged by regulating CD8 ⁺ T cells.

Keywords: anti-CD47; cordycepin; macrophage; scRNA-seq; tumor microenvironment.

Grants and funding

The study was supported by the National Natural Science Foundation Program of PR China (No. 32270955), the Clinical Frontier Technology Project of the Jiangsu Key Research and Development Program (No. BE2022719), the Jiangsu Traditional Chinese Medicine Science and Technology Development Plan Project (No. ZT202115), and the Changzhou Science and Technology Support Projects of Social Development (No. CE20215030).