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

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...

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Autores principales: Feng, Chen, Chen, Rongzhang, Fang, Weiwei, Gao, Xinran, Ying, Hanjie, Zheng, Xiao, Chen, Lujun, Jiang, Jingting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10149837/
https://www.ncbi.nlm.nih.gov/pubmed/37138855
http://dx.doi.org/10.3389/fphar.2023.1144330
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author Feng, Chen
Chen, Rongzhang
Fang, Weiwei
Gao, Xinran
Ying, Hanjie
Zheng, Xiao
Chen, Lujun
Jiang, Jingting
author_facet Feng, Chen
Chen, Rongzhang
Fang, Weiwei
Gao, Xinran
Ying, Hanjie
Zheng, Xiao
Chen, Lujun
Jiang, Jingting
author_sort Feng, Chen
collection PubMed
description 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.
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spelling pubmed-101498372023-05-02 Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer Feng, Chen Chen, Rongzhang Fang, Weiwei Gao, Xinran Ying, Hanjie Zheng, Xiao Chen, Lujun Jiang, Jingting Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2023-04-17 /pmc/articles/PMC10149837/ /pubmed/37138855 http://dx.doi.org/10.3389/fphar.2023.1144330 Text en Copyright © 2023 Feng, Chen, Fang, Gao, Ying, Zheng, Chen and Jiang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Feng, Chen
Chen, Rongzhang
Fang, Weiwei
Gao, Xinran
Ying, Hanjie
Zheng, Xiao
Chen, Lujun
Jiang, Jingting
Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer
title Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer
title_full Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer
title_fullStr Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer
title_full_unstemmed Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer
title_short Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer
title_sort synergistic effect of cd47 blockade in combination with cordycepin treatment against cancer
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10149837/
https://www.ncbi.nlm.nih.gov/pubmed/37138855
http://dx.doi.org/10.3389/fphar.2023.1144330
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