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Sci Rep. 2018 Jul 13;8(1):10668. doi: 10.1038/s41598-018-29048-8.

Novel natural killer cell-mediated cancer immunotherapeutic activity of anisomycin against hepatocellular carcinoma cells.

Author information

1
Bio & Drug Discovery Division, Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology (KRICT), Daejeon, 305-600, Republic of Korea.
2
Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.
3
Department of Animal Biotechnology, Kyungpook National University, Sangju, Gyeongbuk, 37224, Republic of Korea.
4
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
5
Bio & Drug Discovery Division, Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology (KRICT), Daejeon, 305-600, Republic of Korea. redmour0@gmail.com.
6
Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea. redmour0@gmail.com.

Abstract

Despite advances in the clinical management of hepatocellular carcinoma (HCC), this form of cancer remains the second leading cause of cancer-related death worldwide. Currently, there are few treatment options for advanced HCC. Therefore, novel treatment strategies for HCC are required. Here, we described the promising antitumour effects of anisomycin, which exerts both direct killing effects and natural killer cell (NK)-mediated immunotherapeutic effects in HCC. To better elucidate the mechanisms through which anisomycin mediates its antitumour effects, we performed a genome-scale transcriptional analysis. We found that anisomycin treatment of HCC differentially modulated a broad range of immune regulation-associated genes. Among these immune regulation-associated genes, we found that lymphocyte function-associated antigen-3 (LFA-3, also called CD58), whose expression was significantly increased in anisomycin-treated HCC cells, was a critical player in NK-mediated immunotherapeutic effects. Furthermore major histocompatibility complex molecules class I (MHC-I) on HCC cells were also significantly regulated by treatment of anisomycin. Those adhesion molecules like CD58, MHC-I, and ICAM4 should be important for immune synapse formation between NK cells and HCC cells to boost NK-mediated immunotherapeutic effects. Notably, this is the first report of NK-dependent immunomodulatory effects of anisomycin suggesting anisomycin as a novel therapeutic drug for treatment of HCC.

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