PMID- 34377237 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211118 IS - 1943-8141 (Print) IS - 1943-8141 (Electronic) IS - 1943-8141 (Linking) VI - 13 IP - 7 DP - 2021 TI - Combined treatment with epigenetic agents enhances anti-tumor activity of T cells by upregulating the ACRBP expression in hepatocellular carcinoma. PG - 7591-7609 AB - OBJECTIVE: To evaluate the efficacy of combined epigenetic drugs of decitabine (DAC), valproic acid (VPA) and trichostatin A (TSA) on immunotherapy with a murine model of hepatocellular carcinoma (HCC). METHODS: Dendritic cells (DCs) transduced with recombinant lentivirus expressing a cancer-testis antigen, acrosin binding protein (ACRBP), are referred to as DC/ACRBP. CD8(+) T cells were harvested from spleens of C57BL/6 mice and activated by DC/ACRBP. Cytotoxicity of DC/ACRBP-activated T cells was analyzed by cytotoxicity and murine xenograft assays. RESULTS: Cytotoxicity assay results revealed that DC/ACRBP-activated T cells exhibited the highest cytotoxicity against HCC cells pre-treated with triple drugs (DAC+VPA+TSA) compared with dual drugs (DAC+VPA and DAC+TSA) and single drug (DAC, VPA and TSA) respectively. Analyses of RT-PCR and immunoblotting demonstrated that the highest ACRBP expression of HCC cells was induced by the triple drugs compared with the single and dual drugs. These results indicated that DC/ACRBP-activated T cells might be ACRBP-specific lymphocytes, and the augmented cytotoxicity may be dependent on the upregulation of ACRBP expression. These assumptions were further confirmed by xenograft tumor assay. Tumor cells of mice administrated with the triple drugs exhibited increased ACRBP expression compared with those of mice without administration. As expected, DC/ACRBP-activated T cells adopted by mice injected with the triple drugs, compared with those adopted by mice without injection, remarkably impeded growth and facilitated apoptosis of tumor cells. CONCLUSION: These data suggested that combined treatment with DAC, VPA and TSA may enhance the anti-tumor efficacy of ACRBP-specific T cells by upregulating ACRBP expression in HCC. CI - AJTR Copyright (c) 2021. FAU - Ge, Ying-Ying AU - Ge YY AD - Department of Histology and Embryology, School of Pre-Clinical Medicine, Guangxi Medical University Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. AD - Central Laboratory of Pre-Clinical Medicine (Key Laboratory of Guangxi Colleges and Universities), Guangxi Medical University Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. FAU - Zhang, Qing-Mei AU - Zhang QM AD - Department of Histology and Embryology, School of Pre-Clinical Medicine, Guangxi Medical University Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. AD - Central Laboratory of Pre-Clinical Medicine (Key Laboratory of Guangxi Colleges and Universities), Guangxi Medical University Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. FAU - Liu, Chang AU - Liu C AD - Department of Neurosurgery, The First Hospital of Guangxi Medical University Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. FAU - Zeng, Xia AU - Zeng X AD - Department of Histology and Embryology, School of Pre-Clinical Medicine, Guangxi Medical University Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. FAU - Nong, Wei-Xia AU - Nong WX AD - Department of Histology and Embryology, School of Pre-Clinical Medicine, Guangxi Medical University Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. FAU - Chen, Fang AU - Chen F AD - Department of Histology and Embryology, School of Pre-Clinical Medicine, Guangxi Medical University Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. AD - Central Laboratory of Pre-Clinical Medicine (Key Laboratory of Guangxi Colleges and Universities), Guangxi Medical University Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. FAU - Bi, Shui-Qing AU - Bi SQ AD - Department of Histology and Embryology, School of Pre-Clinical Medicine, Guangxi Medical University Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. FAU - Guo, Wen-Wen AU - Guo WW AD - Department of Pathology, The People's Hospital of Guangxi Zhuang Autonomous Region Nanning 530021, People's Republic of China. FAU - Luo, Bin AU - Luo B AD - Department of Histology and Embryology, School of Pre-Clinical Medicine, Guangxi Medical University Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. AD - Central Laboratory of Pre-Clinical Medicine (Key Laboratory of Guangxi Colleges and Universities), Guangxi Medical University Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. FAU - Xie, Xiao-Xun AU - Xie XX AD - Department of Histology and Embryology, School of Pre-Clinical Medicine, Guangxi Medical University Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. AD - Central Laboratory of Pre-Clinical Medicine (Key Laboratory of Guangxi Colleges and Universities), Guangxi Medical University Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. AD - Key Laboratory of Early Prevention and Treatment of Regional High Frequency Tumor (Guangxi Medical University) Ministry of Education, People's Republic of China. LA - eng PT - Journal Article DEP - 20210715 PL - United States TA - Am J Transl Res JT - American journal of translational research JID - 101493030 PMC - PMC8340224 OTO - NOTNLM OT - Decitabine OT - acrosin binding protein OT - cytotoxic T lymphocyte OT - hepatocellular carcinoma OT - trichostatin A OT - valproic acid COIS- None. EDAT- 2021/08/12 06:00 MHDA- 2021/08/12 06:01 PMCR- 2021/07/15 CRDT- 2021/08/11 06:37 PHST- 2020/08/15 00:00 [received] PHST- 2021/03/02 00:00 [accepted] PHST- 2021/08/11 06:37 [entrez] PHST- 2021/08/12 06:00 [pubmed] PHST- 2021/08/12 06:01 [medline] PHST- 2021/07/15 00:00 [pmc-release] PST - epublish SO - Am J Transl Res. 2021 Jul 15;13(7):7591-7609. eCollection 2021.