Antifibrotic Therapy Augments the Antitumor Effects of Vesicular Stomatitis Virus Via Reprogramming Tumor Microenvironment
Solid tumors are characterized by abundant extracellular matrix originating from cancer-associated fibroblasts (CAFs). High collagen content can trigger the collapse of vascular system in the tumor and form physical barrier that eventually impedes the penetration of drug particles and cytotoxic immu...
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| Veröffentlicht in: | Human gene therapy 2022-03, Vol.33 (5-6), p.237-249 |
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| creator | Chen, Yanwei Hu, Shichuan Shu, Yongheng Qi, Zhongbing Zhang, Bin Kuang, Yueting Ma, Jinhu Cheng, Ping |
| description | Solid tumors are characterized by abundant extracellular matrix originating from cancer-associated fibroblasts (CAFs). High collagen content can trigger the collapse of vascular system in the tumor and form physical barrier that eventually impedes the penetration of drug particles and cytotoxic immune cells. Moreover, CAFs is able to promote the enrichment of tumor-associated macrophages (TAMs) and differentiation of myeloid-derived suppressor cells (MDSCs) that work in concert to develop a highly immunosuppressive tumor microenvironment (TME). In this study, we investigated if halofuginone, an antifibrotic drug, can augment the therapeutic effects of oncolytic vesicular stomatitis virus (VSV). The results revealed that halofuginone significantly disrupts the collagen network in tumors and promotes the distribution of VSV and infiltration of CD8
T cells (
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| doi_str_mv | 10.1089/hum.2021.048 |
| format | Article |
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T cells (
< 0.0001). Combined treatment of VSV and halofuginone also modulates the immunosuppressive TME via deletion of TAM, MDSCs, and regulatory T cells (Tregs). Collectively, the combination therapy remarkably inhibits the tumor growth in multiple murine models and prolongs survival of mice. The results demonstrate the clinical potential of halofuginone in combination with oncolytic virus.</description><identifier>ISSN: 1043-0342</identifier><identifier>EISSN: 1557-7422</identifier><identifier>DOI: 10.1089/hum.2021.048</identifier><identifier>PMID: 34405694</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Animal models ; Animals ; Anticancer properties ; Antitumor activity ; Barriers ; CD8 antigen ; CD8-Positive T-Lymphocytes ; Cell differentiation ; Cell Line, Tumor ; Collagen ; Combined treatment ; Cytotoxicity ; Extracellular matrix ; Fibroblasts ; Immune system ; Immunoregulation ; Lymphocytes ; Lymphocytes T ; Macrophages ; Metastases ; Mice ; Neoplasms - therapy ; Oncolysis ; Oncolytic Virotherapy - methods ; Oncolytic Viruses - genetics ; Solid tumors ; Stomatitis ; Suppressor cells ; Tumor Microenvironment ; Tumors ; Vascular system ; Vesicular Stomatitis - therapy ; Vesicular stomatitis Indiana virus ; Viruses</subject><ispartof>Human gene therapy, 2022-03, Vol.33 (5-6), p.237-249</ispartof><rights>Copyright Mary Ann Liebert, Inc. Mar 2022</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c249t-9f80848b9835a532bbc9ed25ed933a3dffcbc62e1746e9b337cc3e6600e7fcd43</citedby><cites>FETCH-LOGICAL-c249t-9f80848b9835a532bbc9ed25ed933a3dffcbc62e1746e9b337cc3e6600e7fcd43</cites><orcidid>0000-0001-5440-5941</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34405694$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Yanwei</creatorcontrib><creatorcontrib>Hu, Shichuan</creatorcontrib><creatorcontrib>Shu, Yongheng</creatorcontrib><creatorcontrib>Qi, Zhongbing</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Kuang, Yueting</creatorcontrib><creatorcontrib>Ma, Jinhu</creatorcontrib><creatorcontrib>Cheng, Ping</creatorcontrib><title>Antifibrotic Therapy Augments the Antitumor Effects of Vesicular Stomatitis Virus Via Reprogramming Tumor Microenvironment</title><title>Human gene therapy</title><addtitle>Hum Gene Ther</addtitle><description>Solid tumors are characterized by abundant extracellular matrix originating from cancer-associated fibroblasts (CAFs). High collagen content can trigger the collapse of vascular system in the tumor and form physical barrier that eventually impedes the penetration of drug particles and cytotoxic immune cells. Moreover, CAFs is able to promote the enrichment of tumor-associated macrophages (TAMs) and differentiation of myeloid-derived suppressor cells (MDSCs) that work in concert to develop a highly immunosuppressive tumor microenvironment (TME). In this study, we investigated if halofuginone, an antifibrotic drug, can augment the therapeutic effects of oncolytic vesicular stomatitis virus (VSV). The results revealed that halofuginone significantly disrupts the collagen network in tumors and promotes the distribution of VSV and infiltration of CD8
T cells (
< 0.0001). Combined treatment of VSV and halofuginone also modulates the immunosuppressive TME via deletion of TAM, MDSCs, and regulatory T cells (Tregs). Collectively, the combination therapy remarkably inhibits the tumor growth in multiple murine models and prolongs survival of mice. The results demonstrate the clinical potential of halofuginone in combination with oncolytic virus.</description><subject>Animal models</subject><subject>Animals</subject><subject>Anticancer properties</subject><subject>Antitumor activity</subject><subject>Barriers</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes</subject><subject>Cell differentiation</subject><subject>Cell Line, Tumor</subject><subject>Collagen</subject><subject>Combined treatment</subject><subject>Cytotoxicity</subject><subject>Extracellular matrix</subject><subject>Fibroblasts</subject><subject>Immune system</subject><subject>Immunoregulation</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Metastases</subject><subject>Mice</subject><subject>Neoplasms - therapy</subject><subject>Oncolysis</subject><subject>Oncolytic Virotherapy - methods</subject><subject>Oncolytic Viruses - genetics</subject><subject>Solid tumors</subject><subject>Stomatitis</subject><subject>Suppressor cells</subject><subject>Tumor Microenvironment</subject><subject>Tumors</subject><subject>Vascular system</subject><subject>Vesicular Stomatitis - therapy</subject><subject>Vesicular stomatitis Indiana virus</subject><subject>Viruses</subject><issn>1043-0342</issn><issn>1557-7422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc9rFDEYhoNYbK29eZaAFw_Omp8zk-NS2ipUBN32GjKZL7spm8maTIT61zdjaw-9fPkIT17e8CD0npIVJb36sithxQijKyL6V-iEStk1nWDsdd2J4A3hgh2jtznfEUK5bLs36JgLQWSrxAn6u55m7_yQ4uwt3uwgmcM9XpdtgGnOeN4BXoi5hJjwhXNg6210-Bayt2VvEv41x2Aq4TO-9aks0-CfcEhxm0wIftrizb_X371NEaY_PsVpSX-HjpzZZzh7Ok_RzeXF5vxrc_3j6tv5-rqxTKi5Ua4nvegH1XNpJGfDYBWMTMKoODd8dM4OtmVAO9GCGjjvrOXQtoRA5-wo-Cn69JhbK_0ukGcdfLaw35sJYsmayZZJ2hPZVfTjC_QuljTVdpq1XHWCsl5V6vMjVf-TcwKnD8kHk-41JXpxoqsTvTjR1UnFPzyFliHA-Az_l8AfAJ85ieE</recordid><startdate>202203</startdate><enddate>202203</enddate><creator>Chen, Yanwei</creator><creator>Hu, Shichuan</creator><creator>Shu, Yongheng</creator><creator>Qi, Zhongbing</creator><creator>Zhang, Bin</creator><creator>Kuang, Yueting</creator><creator>Ma, Jinhu</creator><creator>Cheng, Ping</creator><general>Mary Ann Liebert, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5440-5941</orcidid></search><sort><creationdate>202203</creationdate><title>Antifibrotic Therapy Augments the Antitumor Effects of Vesicular Stomatitis Virus Via Reprogramming Tumor Microenvironment</title><author>Chen, Yanwei ; Hu, Shichuan ; Shu, Yongheng ; Qi, Zhongbing ; Zhang, Bin ; Kuang, Yueting ; Ma, Jinhu ; Cheng, Ping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c249t-9f80848b9835a532bbc9ed25ed933a3dffcbc62e1746e9b337cc3e6600e7fcd43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Anticancer properties</topic><topic>Antitumor activity</topic><topic>Barriers</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes</topic><topic>Cell differentiation</topic><topic>Cell Line, Tumor</topic><topic>Collagen</topic><topic>Combined treatment</topic><topic>Cytotoxicity</topic><topic>Extracellular matrix</topic><topic>Fibroblasts</topic><topic>Immune system</topic><topic>Immunoregulation</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Macrophages</topic><topic>Metastases</topic><topic>Mice</topic><topic>Neoplasms - therapy</topic><topic>Oncolysis</topic><topic>Oncolytic Virotherapy - methods</topic><topic>Oncolytic Viruses - genetics</topic><topic>Solid tumors</topic><topic>Stomatitis</topic><topic>Suppressor cells</topic><topic>Tumor Microenvironment</topic><topic>Tumors</topic><topic>Vascular system</topic><topic>Vesicular Stomatitis - therapy</topic><topic>Vesicular stomatitis Indiana virus</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Yanwei</creatorcontrib><creatorcontrib>Hu, Shichuan</creatorcontrib><creatorcontrib>Shu, Yongheng</creatorcontrib><creatorcontrib>Qi, Zhongbing</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Kuang, Yueting</creatorcontrib><creatorcontrib>Ma, Jinhu</creatorcontrib><creatorcontrib>Cheng, Ping</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Human gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Yanwei</au><au>Hu, Shichuan</au><au>Shu, Yongheng</au><au>Qi, Zhongbing</au><au>Zhang, Bin</au><au>Kuang, Yueting</au><au>Ma, Jinhu</au><au>Cheng, Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antifibrotic Therapy Augments the Antitumor Effects of Vesicular Stomatitis Virus Via Reprogramming Tumor Microenvironment</atitle><jtitle>Human gene therapy</jtitle><addtitle>Hum Gene Ther</addtitle><date>2022-03</date><risdate>2022</risdate><volume>33</volume><issue>5-6</issue><spage>237</spage><epage>249</epage><pages>237-249</pages><issn>1043-0342</issn><eissn>1557-7422</eissn><abstract>Solid tumors are characterized by abundant extracellular matrix originating from cancer-associated fibroblasts (CAFs). High collagen content can trigger the collapse of vascular system in the tumor and form physical barrier that eventually impedes the penetration of drug particles and cytotoxic immune cells. Moreover, CAFs is able to promote the enrichment of tumor-associated macrophages (TAMs) and differentiation of myeloid-derived suppressor cells (MDSCs) that work in concert to develop a highly immunosuppressive tumor microenvironment (TME). In this study, we investigated if halofuginone, an antifibrotic drug, can augment the therapeutic effects of oncolytic vesicular stomatitis virus (VSV). The results revealed that halofuginone significantly disrupts the collagen network in tumors and promotes the distribution of VSV and infiltration of CD8
T cells (
< 0.0001). Combined treatment of VSV and halofuginone also modulates the immunosuppressive TME via deletion of TAM, MDSCs, and regulatory T cells (Tregs). Collectively, the combination therapy remarkably inhibits the tumor growth in multiple murine models and prolongs survival of mice. The results demonstrate the clinical potential of halofuginone in combination with oncolytic virus.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>34405694</pmid><doi>10.1089/hum.2021.048</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-5440-5941</orcidid></addata></record> |
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| subjects | Animal models Animals Anticancer properties Antitumor activity Barriers CD8 antigen CD8-Positive T-Lymphocytes Cell differentiation Cell Line, Tumor Collagen Combined treatment Cytotoxicity Extracellular matrix Fibroblasts Immune system Immunoregulation Lymphocytes Lymphocytes T Macrophages Metastases Mice Neoplasms - therapy Oncolysis Oncolytic Virotherapy - methods Oncolytic Viruses - genetics Solid tumors Stomatitis Suppressor cells Tumor Microenvironment Tumors Vascular system Vesicular Stomatitis - therapy Vesicular stomatitis Indiana virus Viruses |
| title | Antifibrotic Therapy Augments the Antitumor Effects of Vesicular Stomatitis Virus Via Reprogramming Tumor Microenvironment |
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