In situ vaccination followed by intramuscular poly-ICLC injections for the treatment of hepatocellular carcinoma in mouse models
Journal
Pharmacological research
Journal Volume
188
Pages
106646
Date Issued
2023-01-05
Author(s)
Yang, Shih-Feng
Liu, Shin-Yun
Hsu, Yu-Chen
Wu, Meng-Chuan
Chou, Huei-Chi
Chiou, Ling-Ling
Wang, Li-Fang
Sheu, Jin-Chuan
Abstract
The efficacy of treatment for advanced hepatocellular carcinoma (HCC) has remained limited. Polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) is a synthetic double-stranded RNA that serves as a viral mimic and induces an immune response. Intratumoral (IT) poly-ICLC injections can induce an autovaccination effect and prime the immune system, whereas intramuscular (IM) injection of poly-ICLC can attract and maintain tumor-specific cytotoxic T lymphocytes in tumors. We found that IT injection of poly-ICLC upregulated the expression of CD83 and CD86 on conventional type 1 dendritic cells in tumors. Combination therapy with IT followed by IM injections of poly-ICLC significantly inhibited tumor growth and increased the tumor-infiltrating CD8+ T cells in two syngeneic mouse models of HCC. Depletion of CD8+ T cells attenuated the antitumor effect. An IFN-γ enzyme-linked immunospot of purified tumoral CD8+ T cells revealed a significant proportion of tumor-specific T cells. Finally, the sequential poly-ICLC therapy induced abscopal effects in two dual-tumor models. This study provides evidence that the sequential poly-ICLC therapy significantly increased infiltration of tumor-specific CD8+ T cells in the tumors and induced CD8+ T cell-dependent inhibition of tumor growth, as well as abscopal effects.
Subjects
Abscopal effect; Hepatocellular carcinoma; Poly-ICLC; in situ vaccination
SDGs
Type
journal article