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

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.

SUBMITTER: Kim M

PROVIDER: S-EPMC6045618 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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

Kim Miok M Lee Seon-Jin SJ Shin Sangsu S Park Kang-Seo KS Park Sang Yoon SY Lee Chang Hoon CH

Scientific reports 20180713 1

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 mechanis ...[more]

PMID: 30006566

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Project description:BackgroundHepatocellular carcinoma (HCC) is a prevalent tumor that poses a significant threat to human health, with 80% of cases being primary HCC. At present, Early diagnosis and predict prognosis of HCC is challenging and the it is characterized by a high degree of invasiveness, both of which negatively impact patient prognosis. Natural killer cells (NK) play an important role in the development, diagnosis and prognosis of malignant tumors. The potential of NK cell-related genes for evaluating the prognosis of patients with hepatocellular carcinoma remains unexplored. This study aims to address this gap by investigating the association between NK cell-related genes and the prognosis of HCC patients, with the goal of developing a reliable model that can provide novel insights into evaluating the immunotherapy response and prognosis of these patients. This work has the potential to significantly advance our understanding of the complex interplay between immune cells and tumors, and may ultimately lead to improved clinical outcomes for HCC patients.MethodsFor this study, we employed transcriptome expression data from the hepatocellular carcinoma cancer genome map (TCGA-LIHC) to develop a model consisting of NK cell-related genes. To construct the NK cell-related signature (NKRLSig), we utilized a combination of univariate COX regression, Area Under Curve (AUC) LASSO COX regression, and multivariate COX regression. To validate the model, we conducted external validation using the GSE14520 cohort.ResultsWe developed a prognostic model based on 5-NKRLSig (IL18RAP, CHP1, VAMP2, PIC3R1, PRKCD), which divided patients into high- and low-risk groups based on their risk score. The high-risk group was associated with a poor prognosis, and the risk score had good predictive ability across all clinical subgroups. The risk score and stage were found to be independent prognostic indicators for HCC patients when clinical factors were taken into account. We further created a nomogram incorporating the 5-NKRLSig and clinicopathological characteristics, which revealed that patients in the low-risk group had a better prognosis. Moreover, our analysis of immunotherapy and chemotherapy response indicated that patients in the low-risk group were more responsive to immunotherapy.ConclusionThe model that we developed not only sheds light on the regulatory mechanism of NK cell-related genes in HCC, but also has the potential to advance our understanding of immunotherapy for HCC. With its strong predictive capacity, our model may prove useful in evaluating the prognosis of patients and guiding clinical decision-making for HCC patients.

Dataset Information

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

Publications

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

Similar Datasets

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