Oncolytic adenovirus inhibits malignant ascites of advanced ovarian cancer by reprogramming the ascitic immune microenvironment

Malignant ascites frequently occur in patients with advanced ovarian cancer at initial diagnosis, and in almost all cases of relapse, they are closely related to poor prognosis, chemoresistance, and metastasis. To date, effective management strategies have been limited. In this study, we aimed to in...

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Autores principales:	Gang Shi, Pengyi Shi, Yan Yu, Jia Xu, Jinhu Ma, Yong Zhang, Zhexu Dong, Lanlin Shen, Lei Dai, Lin Cheng, Ping Cheng, Hongxin Deng
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	malignant ascites ovarian cancer oncolytic viruses immune microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/b13fbf4f68bb42d88d66d339a8f15964
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spelling	oai:doaj.org-article:b13fbf4f68bb42d88d66d339a8f159642021-11-26T04:35:19ZOncolytic adenovirus inhibits malignant ascites of advanced ovarian cancer by reprogramming the ascitic immune microenvironment2372-770510.1016/j.omto.2021.11.008https://doaj.org/article/b13fbf4f68bb42d88d66d339a8f159642021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2372770521001571https://doaj.org/toc/2372-7705Malignant ascites frequently occur in patients with advanced ovarian cancer at initial diagnosis, and in almost all cases of relapse, they are closely related to poor prognosis, chemoresistance, and metastasis. To date, effective management strategies have been limited. In this study, we aimed to investigate the effects of oncolytic adenovirus (OV) on malignant ascites in a mouse model of advanced ovarian cancer. The results suggested that OV conferred an effective ability to reduce ascites development and prolong overall survival. Further analysis of the ascitic immune microenvironment revealed that OV treatment promoted T cell infiltration, activation, and differentiation into the effector phenotype; reprogrammed macrophages toward the M1-like phenotype; and increased the ratios of both CD8+ T cells to CD4+ T cells and M1 to M2 macrophages. However, immunosuppressive factors such as PD-1, LAG-3, and Tregs emerged after treatment. Combination therapy including OV, CSF-1R inhibitor PLX3397, and anti-PD-1 remarkably delayed the progression of ascites, and combination therapy induced a greater extent of T cell infiltration, proliferation, and activation. This study provides experimental and theoretical evidence for oncolytic virus-based treatment of malignant ascites, which may further contribute to advanced ovarian cancer therapy.Gang ShiPengyi ShiYan YuJia XuJinhu MaYong ZhangZhexu DongLanlin ShenLei DaiLin ChengPing ChengHongxin DengElsevierarticlemalignant ascitesovarian canceroncolytic virusesimmune microenvironmentNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Therapy: Oncolytics, Vol 23, Iss , Pp 488-500 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	malignant ascites ovarian cancer oncolytic viruses immune microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	malignant ascites ovarian cancer oncolytic viruses immune microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Gang Shi Pengyi Shi Yan Yu Jia Xu Jinhu Ma Yong Zhang Zhexu Dong Lanlin Shen Lei Dai Lin Cheng Ping Cheng Hongxin Deng Oncolytic adenovirus inhibits malignant ascites of advanced ovarian cancer by reprogramming the ascitic immune microenvironment
description	Malignant ascites frequently occur in patients with advanced ovarian cancer at initial diagnosis, and in almost all cases of relapse, they are closely related to poor prognosis, chemoresistance, and metastasis. To date, effective management strategies have been limited. In this study, we aimed to investigate the effects of oncolytic adenovirus (OV) on malignant ascites in a mouse model of advanced ovarian cancer. The results suggested that OV conferred an effective ability to reduce ascites development and prolong overall survival. Further analysis of the ascitic immune microenvironment revealed that OV treatment promoted T cell infiltration, activation, and differentiation into the effector phenotype; reprogrammed macrophages toward the M1-like phenotype; and increased the ratios of both CD8+ T cells to CD4+ T cells and M1 to M2 macrophages. However, immunosuppressive factors such as PD-1, LAG-3, and Tregs emerged after treatment. Combination therapy including OV, CSF-1R inhibitor PLX3397, and anti-PD-1 remarkably delayed the progression of ascites, and combination therapy induced a greater extent of T cell infiltration, proliferation, and activation. This study provides experimental and theoretical evidence for oncolytic virus-based treatment of malignant ascites, which may further contribute to advanced ovarian cancer therapy.
format	article
author	Gang Shi Pengyi Shi Yan Yu Jia Xu Jinhu Ma Yong Zhang Zhexu Dong Lanlin Shen Lei Dai Lin Cheng Ping Cheng Hongxin Deng
author_facet	Gang Shi Pengyi Shi Yan Yu Jia Xu Jinhu Ma Yong Zhang Zhexu Dong Lanlin Shen Lei Dai Lin Cheng Ping Cheng Hongxin Deng
author_sort	Gang Shi
title	Oncolytic adenovirus inhibits malignant ascites of advanced ovarian cancer by reprogramming the ascitic immune microenvironment
title_short	Oncolytic adenovirus inhibits malignant ascites of advanced ovarian cancer by reprogramming the ascitic immune microenvironment
title_full	Oncolytic adenovirus inhibits malignant ascites of advanced ovarian cancer by reprogramming the ascitic immune microenvironment
title_fullStr	Oncolytic adenovirus inhibits malignant ascites of advanced ovarian cancer by reprogramming the ascitic immune microenvironment
title_full_unstemmed	Oncolytic adenovirus inhibits malignant ascites of advanced ovarian cancer by reprogramming the ascitic immune microenvironment
title_sort	oncolytic adenovirus inhibits malignant ascites of advanced ovarian cancer by reprogramming the ascitic immune microenvironment
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/b13fbf4f68bb42d88d66d339a8f15964
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Oncolytic adenovirus inhibits malignant ascites of advanced ovarian cancer by reprogramming the ascitic immune microenvironment

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