https://scholars.lib.ntu.edu.tw/handle/123456789/627640
Title: | In situ vaccination followed by intramuscular poly-ICLC injections for the treatment of hepatocellular carcinoma in mouse models | Authors: | Weng, Meng-Tzu Yang, Shih-Feng Liu, Shin-Yun Hsu, Yu-Chen Wu, Meng-Chuan Chou, Huei-Chi Chiou, Ling-Ling JA-DER LIANG Wang, Li-Fang Lee, Hsuan-Shu Sheu, Jin-Chuan |
Keywords: | Abscopal effect; Hepatocellular carcinoma; Poly-ICLC; in situ vaccination | Issue Date: | 5-Jan-2023 | Journal Volume: | 188 | Start page/Pages: | 106646 | Source: | Pharmacological research | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/627640 | ISSN: | 10436618 | DOI: | 10.1016/j.phrs.2023.106646 |
Appears in Collections: | 醫學系 |
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