Intratumoral IL-28B Gene Delivery Elicits Antitumor Effects by Remodeling of the Tumor Microenvironment in H22-Bearing Mice.
J Immunol Res
; 2022: 1345971, 2022.
Article
in En
| MEDLINE
| ID: mdl-35935577
ABSTRACT
IL-28B, belonging to type III interferons (IFN-λs), exhibits a potent antitumor activity with reduced regulated T cells (Tregs) population, yet the effect of IL-28B on the tumor microenvironment (TME) and if IL-28B can downregulate Tregs directly in vitro are still unknown. In this study, we investigated the effects of IL-28B on Tregs in the spleen and TME in H22 tumor-bearing mice and verified the downregulation of IL-28B on Tregs in vitro. We found that rAd-mIL-28B significantly inhibited tumor growth and reduced the frequency of splenic CD4+Foxp3+ T cells. The levels of CXCL13, ICAM-1, MCP-5, and IL-7 in the serum, and the levels of IL-15 and sFasL in the tumor tissue decreased significantly after rAd-mIL-28B treatment relative to rAd-EGFP. Furthermore, the percentage of CD8+ cells in the TME was significantly increased in the rAd-mIL-28B group compared with the untreated group. In vitro, splenocytes were stimulated with anti-CD3/CD28 and IL-2 in the presence of TGF-ß with or without IL-28B for three days and followed by flow cytometric, RT-PCR, and IL-10 production analysis. The results showed that IL-28B significantly reduced the proportion of induced Foxp3+ cells. It demonstrated that IL-28B may be used as a promising immunotherapy strategy against cancer.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tumor Microenvironment
/
Neoplasms
Limits:
Animals
Language:
En
Journal:
J Immunol Res
Year:
2022
Document type:
Article
Affiliation country:
China