Research on anti-tumor mechanism of attenuated Salmonella typhimurium VNP20009
10.16438/j.0513-4870.2023-0376
- VernacularTitle:减毒沙门氏菌VNP20009的抗肿瘤机制研究
- Author:
Te YIN
1
;
Li-na LIU
2
;
Shi-da DONG
1
;
Bao-lian HUANG
1
;
Chen-yang LI
2
;
Zhi-ting CAO
1
;
Zi-chun HUA
1
,
3
,
4
Author Information
1. School of Biopharmacy, China Pharmaceutical University, Nanjing 211198, China
2. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210033, China
3. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210033, China
4. Institute of Pharmaceutical Biotechnology of Jiangsu Industrial Technology Research Institute, Changzhou 213164, China
- Publication Type:Research Article
- Keywords:
VNP20009;
melanoma;
macrophage;
tumor-draining lymph node;
cytotoxic T cell
- From:
Acta Pharmaceutica Sinica
2023;58(9):2700-2706
- CountryChina
- Language:Chinese
-
Abstract:
Attenuated Salmonella typhimurium VNP20009 is a widely used natural oncolytic bacterium, which has great application potential given its unique characteristics, including clinical safety, tumor targeting specificity, and explicit genome sequence. Here, we show that tumor progression can be effectively reduced by intraperitoneal administration with VNP20009 in a mouse model of melanoma (all animal experiments were conducted in accordance with the Animal Ethics Committee of China Pharmaceutical University); co-culture experiment in vitro demonstrated that VNP20009 can induce the polarization of macrophage M1, accompanied by expression of inflammation-related factors; flow cytometry analysis showed that VNP20009 induced the increase of immune cell infiltration in tumor. Further analysis showed that T cells infiltration in tumor-draining lymph node (TDLN) increased, and VNP20009 induced the activation of CD4+ T cells and CD8+ T cells in tumor. Our results demonstrate that VNP20009 treatment significantly inhibited melanoma tumors by remodeling tumor-associated macrophages to an M1-like phenotype, as well as recruiting and activating cytotoxic T cells, combined with its own antigenic activity to exert anti-tumor immunity.
