siRNA targeting PD-L1 delivered with attenuated Salmonella enhanced the anti-tumor effect of lenvatinib on mice bearing Hepatocellular carcinoma.
Int Immunopharmacol
; 111: 109127, 2022 Oct.
Article
in En
| MEDLINE
| ID: mdl-35964407
ABSTRACT
Hepatocellular carcinoma (HCC) is a primary liver cancer representing serious harm to human health. The effective treatment of HCC is challenging. Lenvatinib is an inhibitor of polytyrosine kinase that exerts an effect against HCC by blocking the VEGF signaling pathway. However, its efficacy in most patients remains unsatisfactory. The factors influencing tumorigenesis are diverse; thus, combined treatment is an important strategy against tumors. Programmed death ligand-1 (PD-L1), which binds to programmed death-1 (PD-1), significantly compromises the anti-tumor effect of T cells. Therefore, we designed a siRNA-PD-L1 and delivered it using attenuated Salmonella, and its synergistic effects with Lenvatinib against HCC were evaluated. The results showed that the combination of Lenvatinib and siRNA-PD-L1 inhibited tumor growth in H22 tumor-bearing mice, arrested cell proliferation, and increased cell apoptosis in the tumor. The combination treatment synergistically inhibited the expression of VEGF and PD-L1 and contributed to the increase in T-cell infiltration in the tumor tissues and the ratio of T cells in the spleen. Furthermore, the combination treatment increased the number of granzyme B+ T cells, indicating a significantly improved anti-tumor immunity in mice. Therefore, this combination might be a potential novel strategy for HCC treatment.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Hepatocellular
/
Liver Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Int Immunopharmacol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Year:
2022
Document type:
Article