Oncolytic spore eruption virus encoding IL-7 enhances killing activity of liver cancer by activating CD8+T cells
10.3969/j.issn.1000-484X.2024.01.018
- VernacularTitle:编码IL-7的溶瘤疱疹病毒通过激活CD8+T细胞增强对肝癌的杀伤活性
- Author:
Dongming LI
1
;
Peng LI
;
Lu LU
;
Xueguo WANG
;
Taicheng WANG
;
Hongyan ZHAO
Author Information
1. 海南医学院第二附属医院肝胆胰腺外科,海口 570100
- Keywords:
Liver cancer;
Oncolytic virus;
Herpes simplex virus;
IL-7;
T cells
- From:
Chinese Journal of Immunology
2024;40(1):122-126
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate whether IL-7-secreting oncolytic herpes simplex virus(HSV)could activate CD8+T cells and inhibit the growth of hepatocellular carcinoma.Methods:The expression of IL-7 was detected by Western blot.The in vitro cleavage of tumor cells by tumor oncolytic virus HSV and HSV-IL-7 were detected by crystal violet staining.The tumor inhibition ability of HSV-IL-7 and HSV were detected in subcutaneous transplanted tumor model.Levels of IL-7,IFN-γ and TNF-α in serum and tumor tissues were determined by ELISA.The infiltration of CD8+T cells in tumor tissues was detected by immunohistochemistry.Flow cytometry was used to detect Granzyme B secretion in CD8+T cells infiltrated by tumor.Results:Tumor cells infected with HSV-IL-7 expressed high level of IL-7.Both HSV and HSV-IL-7 can effectively lyse B16-F10,CT-26 and H22 tumor cell lines in a dose-dependent manner in vitro.HSV-IL-7 could significantly inhibit the growth of H22 hepatoma cells in vivo(P<0.01)and prolong the survival time of tumor-bearing mice(P<0.001).HSV-IL-7 could significantly increase the IL-7 content in tumor sites(P<0.000 1),and effectively increase the number of tumor infiltrating CD8+T cells(P<0.001).HSV-IL-7 significantly enhanced Granzyme B secretion of tumor-infiltrating CD8+T cells and IFN-γ and TNF-α in tumor tissues(P<0.000 1).Conclusion:HSV-IL-7 has well tumor inhibition activity in vivo and in vitro.It also can activate the anti-tumor activity of CD8+T cells in vivo by secreting IL-7,inhibit tumor growth and prolong the survival time of tumor-bearing mice.
