Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA933163 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23382232_1.fastq.gz | Fastqsanger.gz | |||
| SRR23382232_2.fastq.gz | Fastqsanger.gz | |||
| SRR23382233_1.fastq.gz | Fastqsanger.gz | |||
| SRR23382233_2.fastq.gz | Fastqsanger.gz |
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Project description:Cordycepin was widely considered as a direct tumor-suppressive drug, however, and as of now few studies have been presented to investigate the effect of cordycepin therapy to the tumor microenvironment (TME). In our study, we demonstrated that cordycepin would decrease the function of M1-like macrophage in TME, and also contribute to macrophage polarization (M2-macrophage). Herein, we tried to establish a combined therapeutic strategy of cordycepin and anti-CD47 antibody. Using single cell RNA sequencing, we improved that the combined treatment would significantly increase the effect of cordycepin, which would reactivate macrophages and reverse macrophage polarization. And then, the combined treatment would regulate the proportion of CD8+T cells to increase the PFS for digestive tract malignancy patients. Finally, Flow cytometry was used to validate the change of percentage for TAM and TIL. Our finding suggests the combined treatment of cordycepin and anti-CD47 mAb could significantly increase tumor suppression, which could increase M1-macrophage and decrease M2-macrophage. The PFS for digestive tract malignancy patients would be increased though regulation of CD8+T cells.
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Project 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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