Yang, Shih-FengShih-FengYangMENG-TZU WENGJA-DER LIANGChiou, Ling-LingLing-LingChiouHsu, Yu-ChenYu-ChenHsuLee, Ying-TeYing-TeLeeLiu, Shin-YunShin-YunLiuWu, Meng-ChuanMeng-ChuanWuChou, Huei-ChiHuei-ChiChouWang, Li-FangLi-FangWangSHU-HAN YULee, Hsuan-ShuHsuan-ShuLeeSheu, Jin-ChuanJin-ChuanSheu2023-05-032023-05-032023-04-2203043835https://scholars.lib.ntu.edu.tw/handle/123456789/630691https://pubmed.ncbi.nlm.nih.gov/37088327/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.enCancer vaccine; Combination immunotherapy; Long peptide; Next generation sequencing; Poly-ICLC[SDGs]SDG3journal article10.1016/j.canlet.2023.216192370883272-s2.0-85153492237https://api.elsevier.com/content/abstract/scopus_id/85153492237