MENG-TZU WENGYang, Shih-FengShih-FengYangLiu, Shin-YunShin-YunLiuHsu, Yu-ChenYu-ChenHsuWu, Meng-ChuanMeng-ChuanWuChou, Huei-ChiHuei-ChiChouChiou, Ling-LingLing-LingChiouJA-DER LIANGWang, Li-FangLi-FangWangSheu, Jin-ChuanJin-ChuanSheuLee, Hsuan-ShuHsuan-ShuLee2023-02-062023-02-062023-01-0510436618https://scholars.lib.ntu.edu.tw/handle/123456789/627640The 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.enAbscopal effect; Hepatocellular carcinoma; Poly-ICLC; in situ vaccination[SDGs]SDG3journal article10.1016/j.phrs.2023.106646366216192-s2.0-85146574853https://api.elsevier.com/content/abstract/scopus_id/85146574853