Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment

Abstract There is an urgent need for novel effective treatment for hepatocellular carcinoma (HCC). Oncolytic viruses (OVs) not only directly lyse malignant cells, but also induce potent antitumour immune responses. The potency and precise mechanisms of antitumour immune activation by attenuated meas...

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Autores principales:	Aiping Chen, Yonghui Zhang, Gang Meng, Dengxu Jiang, Hailin Zhang, Meihong Zheng, Mao Xia, Aiqin Jiang, Junhua Wu, Christian Beltinger, Jiwu Wei
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2dd7872029554af68f3446feb9d188c8
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spelling	oai:doaj.org-article:2dd7872029554af68f3446feb9d188c82021-12-02T11:52:42ZOncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment10.1038/s41598-017-05500-z2045-2322https://doaj.org/article/2dd7872029554af68f3446feb9d188c82017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05500-zhttps://doaj.org/toc/2045-2322Abstract There is an urgent need for novel effective treatment for hepatocellular carcinoma (HCC). Oncolytic viruses (OVs) not only directly lyse malignant cells, but also induce potent antitumour immune responses. The potency and precise mechanisms of antitumour immune activation by attenuated measles virus remain unclear. In this study, we investigated the potency of the measles virus vaccine strain Edmonston (MV-Edm) in improving adoptive CD8+NKG2D+ cells for HCC treatment. We show that MV-Edm-infected HCC enhanced the antitumour activity of CD8+NKG2D+ cells, mediated by at least three distinct mechanisms. First, MV-Edm infection compelled HCC cells to express the specific NKG2D ligands MICA/B, which may contribute to the activation of CD8+NKG2D+ cells. Second, MV-Edm-infected HCC cells stimulated CD8+NKG2D+ cells to express high level of FasL resulting in enhanced induction of apoptosis. Third, intratumoural administration of MV-Edm enhanced infiltration of intravenously injected CD8+NKG2D+ cells. Moreover, we found that MV-Edm and adoptive CD8+NKG2D+ cells, either administered alone or combined, upregulated the immune suppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) in HCC. Elimination of IDO1 by fludarabine enhanced antitumour responses. Taken together, our data provide a novel and clinically relevant strategy for treatment of HCC.Aiping ChenYonghui ZhangGang MengDengxu JiangHailin ZhangMeihong ZhengMao XiaAiqin JiangJunhua WuChristian BeltingerJiwu WeiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aiping Chen Yonghui Zhang Gang Meng Dengxu Jiang Hailin Zhang Meihong Zheng Mao Xia Aiqin Jiang Junhua Wu Christian Beltinger Jiwu Wei Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment
description	Abstract There is an urgent need for novel effective treatment for hepatocellular carcinoma (HCC). Oncolytic viruses (OVs) not only directly lyse malignant cells, but also induce potent antitumour immune responses. The potency and precise mechanisms of antitumour immune activation by attenuated measles virus remain unclear. In this study, we investigated the potency of the measles virus vaccine strain Edmonston (MV-Edm) in improving adoptive CD8+NKG2D+ cells for HCC treatment. We show that MV-Edm-infected HCC enhanced the antitumour activity of CD8+NKG2D+ cells, mediated by at least three distinct mechanisms. First, MV-Edm infection compelled HCC cells to express the specific NKG2D ligands MICA/B, which may contribute to the activation of CD8+NKG2D+ cells. Second, MV-Edm-infected HCC cells stimulated CD8+NKG2D+ cells to express high level of FasL resulting in enhanced induction of apoptosis. Third, intratumoural administration of MV-Edm enhanced infiltration of intravenously injected CD8+NKG2D+ cells. Moreover, we found that MV-Edm and adoptive CD8+NKG2D+ cells, either administered alone or combined, upregulated the immune suppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) in HCC. Elimination of IDO1 by fludarabine enhanced antitumour responses. Taken together, our data provide a novel and clinically relevant strategy for treatment of HCC.
format	article
author	Aiping Chen Yonghui Zhang Gang Meng Dengxu Jiang Hailin Zhang Meihong Zheng Mao Xia Aiqin Jiang Junhua Wu Christian Beltinger Jiwu Wei
author_facet	Aiping Chen Yonghui Zhang Gang Meng Dengxu Jiang Hailin Zhang Meihong Zheng Mao Xia Aiqin Jiang Junhua Wu Christian Beltinger Jiwu Wei
author_sort	Aiping Chen
title	Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment
title_short	Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment
title_full	Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment
title_fullStr	Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment
title_full_unstemmed	Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment
title_sort	oncolytic measles virus enhances antitumour responses of adoptive cd8+nkg2d+ cells in hepatocellular carcinoma treatment
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2dd7872029554af68f3446feb9d188c8
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Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment

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