ORFV infection enhances CXCL16 secretion and causes oncolysis of lung cancer cells through immunogenic apoptosis

Oncolytic viruses have been emerging as a promising therapeutic option for cancer patients, including lung cancer. Orf virus (ORFV), a DNA parapoxvirus, can infect its natural ungulate hosts and transmit into humans. Moreover, the ORFV has advantages of low toxicity, high targeted, self-amplificatio...

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Main Authors: Ruixue Wang, Jingying Mo, Xiaoshan Luo, Guixian Zhang, Fang Liu, Shuhong Luo
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2022.910466/full
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author Ruixue Wang
Jingying Mo
Xiaoshan Luo
Guixian Zhang
Fang Liu
Shuhong Luo
author_facet Ruixue Wang
Jingying Mo
Xiaoshan Luo
Guixian Zhang
Fang Liu
Shuhong Luo
author_sort Ruixue Wang
collection DOAJ
description Oncolytic viruses have been emerging as a promising therapeutic option for cancer patients, including lung cancer. Orf virus (ORFV), a DNA parapoxvirus, can infect its natural ungulate hosts and transmit into humans. Moreover, the ORFV has advantages of low toxicity, high targeted, self-amplification and can induce potent Th1-like immunity. This study explored the therapeutic potential of ORFV infection for human lung cancer therapy and investigated the molecular mechanisms. We used a previously described ORFV NA1/11 strain and tested the oncolysis of ORFV NA1/11 in two lines of lung cancer cells in vitro and in vivo. Treatment of both cell lines with ORFV NA1/11 resulted in a decrease in cell viability by inducing cell cycle arrest in G2/M phase, suppressing cyclin B1 expression and increasing their apoptosis in a caspase-dependent manner. The ORFV NA1/11-infected lung cancer cells were highly immunogenic. Evidently, ORFV NA1/11 infection of lung cancer cells induced oncolysis of tumor cells to release danger-associated molecular patterns, and promoted dendritic cell maturation, and CD8 T cell infiltration in the tumors by enhancing CXCL16 secretion. These findings may help to understand the molecular mechanisms of ORFV oncolysis and aid in the development of novel therapies for lung cancer.
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spelling doaj.art-b7096c3d6ba549e096c09a72402c8de82022-12-22T00:45:33ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-07-011210.3389/fcimb.2022.910466910466ORFV infection enhances CXCL16 secretion and causes oncolysis of lung cancer cells through immunogenic apoptosisRuixue Wang0Jingying Mo1Xiaoshan Luo2Guixian Zhang3Fang Liu4Shuhong Luo5Department of Basic Medical Sciences, School of Medicine, Foshan University, Foshan, ChinaDepartment of Laboratory Medicine, School of Medicine, Foshan University, Foshan, ChinaDepartment of Laboratory Medicine, School of Medicine, Foshan University, Foshan, ChinaDepartment of Basic Medical Sciences, School of Medicine, Foshan University, Foshan, ChinaDepartment of Basic Medical Sciences, School of Medicine, Foshan University, Foshan, ChinaDepartment of Laboratory Medicine, School of Medicine, Foshan University, Foshan, ChinaOncolytic viruses have been emerging as a promising therapeutic option for cancer patients, including lung cancer. Orf virus (ORFV), a DNA parapoxvirus, can infect its natural ungulate hosts and transmit into humans. Moreover, the ORFV has advantages of low toxicity, high targeted, self-amplification and can induce potent Th1-like immunity. This study explored the therapeutic potential of ORFV infection for human lung cancer therapy and investigated the molecular mechanisms. We used a previously described ORFV NA1/11 strain and tested the oncolysis of ORFV NA1/11 in two lines of lung cancer cells in vitro and in vivo. Treatment of both cell lines with ORFV NA1/11 resulted in a decrease in cell viability by inducing cell cycle arrest in G2/M phase, suppressing cyclin B1 expression and increasing their apoptosis in a caspase-dependent manner. The ORFV NA1/11-infected lung cancer cells were highly immunogenic. Evidently, ORFV NA1/11 infection of lung cancer cells induced oncolysis of tumor cells to release danger-associated molecular patterns, and promoted dendritic cell maturation, and CD8 T cell infiltration in the tumors by enhancing CXCL16 secretion. These findings may help to understand the molecular mechanisms of ORFV oncolysis and aid in the development of novel therapies for lung cancer.https://www.frontiersin.org/articles/10.3389/fcimb.2022.910466/fullOrf virus (ORFV)lung cancerapoptosisimmunogenic cell death (ICD)CXCL16
spellingShingle Ruixue Wang
Jingying Mo
Xiaoshan Luo
Guixian Zhang
Fang Liu
Shuhong Luo
ORFV infection enhances CXCL16 secretion and causes oncolysis of lung cancer cells through immunogenic apoptosis
Frontiers in Cellular and Infection Microbiology
Orf virus (ORFV)
lung cancer
apoptosis
immunogenic cell death (ICD)
CXCL16
title ORFV infection enhances CXCL16 secretion and causes oncolysis of lung cancer cells through immunogenic apoptosis
title_full ORFV infection enhances CXCL16 secretion and causes oncolysis of lung cancer cells through immunogenic apoptosis
title_fullStr ORFV infection enhances CXCL16 secretion and causes oncolysis of lung cancer cells through immunogenic apoptosis
title_full_unstemmed ORFV infection enhances CXCL16 secretion and causes oncolysis of lung cancer cells through immunogenic apoptosis
title_short ORFV infection enhances CXCL16 secretion and causes oncolysis of lung cancer cells through immunogenic apoptosis
title_sort orfv infection enhances cxcl16 secretion and causes oncolysis of lung cancer cells through immunogenic apoptosis
topic Orf virus (ORFV)
lung cancer
apoptosis
immunogenic cell death (ICD)
CXCL16
url https://www.frontiersin.org/articles/10.3389/fcimb.2022.910466/full
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