An oncolytic HSV-1 armed with Visfatin enhances antitumor effects by remodeling tumor microenvironment against murine pancreatic cancer.

Autor: Zhao J; State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin, China., Wang H; State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin, China., Chen J; State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin, China., Wang C; State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin, China., Gong N; State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin, China., Zhou F; State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin, China., Li X; State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin, China., Cao Y; State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin, China; Nankai International Advanced Research Institute (Shenzhen Futian), Nankai University, Shenzhen, China., Zhang H; State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin, China., Wang W; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China., Zheng H; State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin, China., Zhang C; State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin, China; Nankai International Advanced Research Institute (Shenzhen Futian), Nankai University, Shenzhen, China. Electronic address: cz912@nankai.edu.cn.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Jul 23; Vol. 718, pp. 149931. Date of Electronic Publication: 2024 Apr 12.
DOI: 10.1016/j.bbrc.2024.149931
Abstrakt: Oncolytic viruses (OVs) have shown potential in converting a "cold" tumor into a "hot" one and exhibit effectiveness in various cancer types. However, only a subset of patients respond to oncolytic virotherapy. It is important to understand the resistance mechanisms to OV treatment in pancreatic ductal adenocarcinoma (PDAC) to engineer oncolytic viruses. In this study, we used transcriptome RNA sequencing (RNA-seq) to identify Visfatin, which was highly expressed in the responsive tumors following OV treatment. To explore the antitumor efficacy, we modified OV-mVisfatin, which effectively inhibited tumor growth. For the first time, we revealed that Visfatin promoted the antitumor efficacy of OV by remodeling the tumor microenvironment, which involved enhancing CD8 + T cell and DC cell infiltration and activation, repolarizing macrophages towards the M1-like phenotype, and decreasing T reg cells using single-cell RNA sequencing (scRNA-seq) and flow cytometry. Furthermore, PD-1 blockade significantly enhanced OV-mVisfatin antitumor efficacy, offering a promising new therapeutic strategy for PDAC.
Competing Interests: Declaration of competing interest We declared that There is No conflict of interest for this paper.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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