https://scholars.lib.ntu.edu.tw/handle/123456789/630691
標題: | Neoantigen vaccination augments antitumor effects of anti-PD-1 on mouse hepatocellular carcinoma | 作者: | Yang, Shih-Feng Weng, Meng-Tzu JA-DER LIANG Chiou, Ling-Ling Hsu, Yu-Chen Lee, Ying-Te Liu, Shin-Yun Wu, Meng-Chuan Chou, Huei-Chi Wang, Li-Fang SHU-HAN YU Lee, Hsuan-Shu Sheu, Jin-Chuan |
關鍵字: | Cancer vaccine; Combination immunotherapy; Long peptide; Next generation sequencing; Poly-ICLC | 公開日期: | 22-四月-2023 | 卷: | 563 | 來源出版物: | Cancer letters | 摘要: | Immune checkpoint inhibitors are groundbreaking resources for cancer therapy. However, only a few patients with hepatocellular carcinoma (HCC) have shown positive responses to anti-PD-1 therapy. Neoantigens are sequence-altered proteins resulting from somatic mutations in cancer. This study identified the neoantigens of Hep-55.1C and Dt81 Hepa1-6 HCCs by comparing their whole exome sequences with those of a normal C57BL/6 mouse liver. Immunogenic long peptides were pooled as peptide vaccines. The vaccination elicited tumor-reactive immune responses in C57BL/6 mice, as demonstrated by IFN-γ ELISPOT and an in vitro killing assay of splenocytes. In the treatment of three mouse HCC models, combined neoantigen vaccination and anti-PD-1 resulted in more significant tumor regression than monotherapies. Flow cytometry of the tumor-infiltrating lymphocytes showed decreased Treg cells and monocytic myeloid-derived suppressor cells, increased CD8+ T cells, enhanced granzyme B expression, and reduced exhaustion-related markers PD-1 and Lag-3 on CD8+ T cells in the combination group. These findings provide a strong rationale for conducting clinical studies of using neoantigen vaccination in combination with anti-PD-1 to treat patients with HCC. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/630691 | ISSN: | 03043835 | DOI: | 10.1016/j.canlet.2023.216192 |
顯示於: | 生物科技研究所 |
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