Cordycepin enhances the Anticancer efficacy of PD-L1 blockade by modulating the tumor microenvironment of colon cancer

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY European journal of pharmacology Pub Date : 2024-11-01 DOI:10.1016/j.ejphar.2024.177089

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

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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.

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虫草素通过调节结肠癌的肿瘤微环境增强 PD-L1 阻断剂的抗癌疗效

背景研究发现，PD-L1 阻断剂可有效治疗多种恶性肿瘤。联合疗法可提供更好的治疗效果。目的：本研究旨在确定抗 PD-L1 抗体和虫草素联合治疗肿瘤的疗效：方法：采用单细胞RNA测序分析联合治疗的机制：结果：抗PD-L1抗体和虫草素联合治疗通过调节T细胞比例和改善CD8+T细胞功能，显著抑制肿瘤生长。此外，虫草素还能促进II型巨噬细胞重编程为I型巨噬细胞，流式细胞仪分析证实了这一过程的内在机制：我们的研究结果表明，抗 PD-L1 和虫草素的联合用药通过调节 T 细胞的比例和 II 型巨噬细胞的重编程，有效抑制了肿瘤的生长。

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来源期刊

European journal of pharmacology 医学-药学

CiteScore

9.00

自引率

0.00%

发文量

572

审稿时长

34 days

期刊介绍： The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.