Inhibition of IL-17A in tumor microenvironment augments cytotoxicity of tumor-infiltrating lymphocytes in tumor-bearing mice
It remains controversial whether IL-17A promotes or inhibits cancer progression. We hypothesized that IL-17A that is locally produced in the tumor microenvironment has an important role in angiogenesis and tumor immunity. We investigated the effect of inhibiting IL-17A at tumor sites on tumor growth...
Gespeichert in:
| Veröffentlicht in: | PloS one 2013-01, Vol.8 (1), p.e53131 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 1 |
| container_start_page | e53131 |
| container_title | PloS one |
| container_volume | 8 |
| creator | Hayata, Keiji Iwahashi, Makoto Ojima, Toshiyasu Katsuda, Masahiro Iida, Takeshi Nakamori, Mikihito Ueda, Kentaro Nakamura, Masaki Miyazawa, Motoki Tsuji, Toshiaki Yamaue, Hiroki |
| description | It remains controversial whether IL-17A promotes or inhibits cancer progression. We hypothesized that IL-17A that is locally produced in the tumor microenvironment has an important role in angiogenesis and tumor immunity. We investigated the effect of inhibiting IL-17A at tumor sites on tumor growth and on local and systemic anti-tumor immunity. MC38 or B16 cells were inoculated subcutaneously into mice, and intratumoral injection of an adenovirus vector expressing siRNA against the mouse IL-17A gene (Ad-si-IL-17) significantly inhibited tumor growth in both tumor models compared with control mice. Inhibition of IL-17A at tumor sites significantly suppressed CD31, MMP9, and VEGF expression in tumor tissue. The cytotoxic activity of CD8(+) T cells from tumor-infiltrating lymphocytes in mice treated with Ad-si-IL-17 was significantly higher than in control mice; however, CD8(+) T cells from splenocytes had similar activity levels. Suppression of IL-17A at tumor sites led to a Th1-dominant environment, and moreover, eliminated myeloid-derived suppressor cells and regulatory T cells at tumor sites but not in splenocytes. In conclusion, blockade of IL-17A at tumor sites helped suppress tumor growth by inhibiting angiogenesis as well as cytotoxic T lymphocytes activation at tumor sites. |
| doi_str_mv | 10.1371/journal.pone.0053131 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1327899247</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A478883629</galeid><doaj_id>oai_doaj_org_article_5af5c23474f74ca48a5e896726e677bb</doaj_id><sourcerecordid>A478883629</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-44f67b8791c89ec61f401756025352408851f9346e68737cabe1510a06e6b6aa3</originalsourceid><addsrcrecordid>eNqNk1uL1DAUx4so7rr6DUQLguhDx6a59kVYFi8DAwveXkOaSTsZ0mRM0mUH_PCmO91hKvsgeUhIfud_cm5Z9hKUCwAp-LB1g7fCLHbOqkVZYgggeJSdgxpWBalK-PjkfJY9C2E7QoyQp9lZBSGtCMbn2Z-l3ehGR-1s7tp8uSoAvcy1zePQO5_3Wnqn7I32zvbKxlwM3biHXO6ji-5WSx33o-UdX2jbahO9iNp2udn3u41LoApHxaJRwo-PSVk9z560wgT1Ytovsp-fP_24-lqsrr8sry5XhaSYxQKhltCG0RpIVitJQItKQDEpKwxxhUrGMGhriIgijEIqRaMABqUo00VDhIAX2euD7s64wKfEBQ5gRVldV4gmYnkg1k5s-c7rXvg9d0LzuwvnOy581NIojkWLZQURRS1FUiAmsGI1SflUhNKmSVofJ29D06u1TOnywsxE5y9Wb3jnbjjEKSZaJ4F3k4B3vwcVIu91kMoYYZUb0r8rBimEmJUJffMP-nB0E9WJFECqkUt-5SjKLxFljEFSjW4XD1BprVUqVuqyVFo1N3g_M0hMVLexE0MIfPn92_-z17_m7NsTdqOEiZvgzDA2aZiD6ACmJg3Bq_aYZFDycUjus8HHIeHTkCSzV6cFOhrdTwX8C84MDTo</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1327899247</pqid></control><display><type>article</type><title>Inhibition of IL-17A in tumor microenvironment augments cytotoxicity of tumor-infiltrating lymphocytes in tumor-bearing mice</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Hayata, Keiji ; Iwahashi, Makoto ; Ojima, Toshiyasu ; Katsuda, Masahiro ; Iida, Takeshi ; Nakamori, Mikihito ; Ueda, Kentaro ; Nakamura, Masaki ; Miyazawa, Motoki ; Tsuji, Toshiaki ; Yamaue, Hiroki</creator><contributor>Gao, Jian-Xin</contributor><creatorcontrib>Hayata, Keiji ; Iwahashi, Makoto ; Ojima, Toshiyasu ; Katsuda, Masahiro ; Iida, Takeshi ; Nakamori, Mikihito ; Ueda, Kentaro ; Nakamura, Masaki ; Miyazawa, Motoki ; Tsuji, Toshiaki ; Yamaue, Hiroki ; Gao, Jian-Xin</creatorcontrib><description>It remains controversial whether IL-17A promotes or inhibits cancer progression. We hypothesized that IL-17A that is locally produced in the tumor microenvironment has an important role in angiogenesis and tumor immunity. We investigated the effect of inhibiting IL-17A at tumor sites on tumor growth and on local and systemic anti-tumor immunity. MC38 or B16 cells were inoculated subcutaneously into mice, and intratumoral injection of an adenovirus vector expressing siRNA against the mouse IL-17A gene (Ad-si-IL-17) significantly inhibited tumor growth in both tumor models compared with control mice. Inhibition of IL-17A at tumor sites significantly suppressed CD31, MMP9, and VEGF expression in tumor tissue. The cytotoxic activity of CD8(+) T cells from tumor-infiltrating lymphocytes in mice treated with Ad-si-IL-17 was significantly higher than in control mice; however, CD8(+) T cells from splenocytes had similar activity levels. Suppression of IL-17A at tumor sites led to a Th1-dominant environment, and moreover, eliminated myeloid-derived suppressor cells and regulatory T cells at tumor sites but not in splenocytes. In conclusion, blockade of IL-17A at tumor sites helped suppress tumor growth by inhibiting angiogenesis as well as cytotoxic T lymphocytes activation at tumor sites.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0053131</identifier><identifier>PMID: 23372655</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenoviridae - genetics ; Adenoviruses ; Advertising executives ; Analysis ; Angiogenesis ; Animal models ; Animals ; Biology ; Cancer ; Cancer treatment ; CD8 antigen ; Cell activation ; Cell Line, Tumor ; Cloning ; Colorectal cancer ; Cytokines ; Cytotoxicity ; Gelatinase B ; Gene Expression Regulation, Neoplastic ; Genetic Vectors ; Immunity ; Immunoregulation ; Inflammation ; Inhibition ; Injections, Intralesional ; Interleukin 17 ; Interleukin-17 - antagonists & inhibitors ; Interleukin-17 - genetics ; Interleukin-17 - immunology ; Laboratory animals ; Liver cancer ; Lung cancer ; Lymphocytes ; Lymphocytes T ; Lymphocytes, Tumor-Infiltrating - immunology ; Lymphocytes, Tumor-Infiltrating - pathology ; Matrix Metalloproteinase 9 - genetics ; Matrix Metalloproteinase 9 - immunology ; Medical research ; Medicine ; Melanoma ; Melanoma, Experimental - blood supply ; Melanoma, Experimental - genetics ; Melanoma, Experimental - metabolism ; Melanoma, Experimental - pathology ; Mice ; Mice, Inbred C57BL ; Neovascularization, Pathologic ; Ovarian cancer ; Penicillin ; Platelet Endothelial Cell Adhesion Molecule-1 - genetics ; Platelet Endothelial Cell Adhesion Molecule-1 - immunology ; RNA, Small Interfering - genetics ; Rodents ; siRNA ; Skin cancer ; Skin Neoplasms - blood supply ; Skin Neoplasms - genetics ; Skin Neoplasms - metabolism ; Skin Neoplasms - pathology ; Splenocytes ; Studies ; Suppressor cells ; Surgery ; T cells ; T-Lymphocytes, Cytotoxic - immunology ; T-Lymphocytes, Cytotoxic - pathology ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - pathology ; Toxicity ; Tumor Microenvironment - genetics ; Tumor-infiltrating lymphocytes ; Tumors ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - immunology</subject><ispartof>PloS one, 2013-01, Vol.8 (1), p.e53131</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Hayata et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Hayata et al 2013 Hayata et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-44f67b8791c89ec61f401756025352408851f9346e68737cabe1510a06e6b6aa3</citedby><cites>FETCH-LOGICAL-c758t-44f67b8791c89ec61f401756025352408851f9346e68737cabe1510a06e6b6aa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556079/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556079/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23372655$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Gao, Jian-Xin</contributor><creatorcontrib>Hayata, Keiji</creatorcontrib><creatorcontrib>Iwahashi, Makoto</creatorcontrib><creatorcontrib>Ojima, Toshiyasu</creatorcontrib><creatorcontrib>Katsuda, Masahiro</creatorcontrib><creatorcontrib>Iida, Takeshi</creatorcontrib><creatorcontrib>Nakamori, Mikihito</creatorcontrib><creatorcontrib>Ueda, Kentaro</creatorcontrib><creatorcontrib>Nakamura, Masaki</creatorcontrib><creatorcontrib>Miyazawa, Motoki</creatorcontrib><creatorcontrib>Tsuji, Toshiaki</creatorcontrib><creatorcontrib>Yamaue, Hiroki</creatorcontrib><title>Inhibition of IL-17A in tumor microenvironment augments cytotoxicity of tumor-infiltrating lymphocytes in tumor-bearing mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>It remains controversial whether IL-17A promotes or inhibits cancer progression. We hypothesized that IL-17A that is locally produced in the tumor microenvironment has an important role in angiogenesis and tumor immunity. We investigated the effect of inhibiting IL-17A at tumor sites on tumor growth and on local and systemic anti-tumor immunity. MC38 or B16 cells were inoculated subcutaneously into mice, and intratumoral injection of an adenovirus vector expressing siRNA against the mouse IL-17A gene (Ad-si-IL-17) significantly inhibited tumor growth in both tumor models compared with control mice. Inhibition of IL-17A at tumor sites significantly suppressed CD31, MMP9, and VEGF expression in tumor tissue. The cytotoxic activity of CD8(+) T cells from tumor-infiltrating lymphocytes in mice treated with Ad-si-IL-17 was significantly higher than in control mice; however, CD8(+) T cells from splenocytes had similar activity levels. Suppression of IL-17A at tumor sites led to a Th1-dominant environment, and moreover, eliminated myeloid-derived suppressor cells and regulatory T cells at tumor sites but not in splenocytes. In conclusion, blockade of IL-17A at tumor sites helped suppress tumor growth by inhibiting angiogenesis as well as cytotoxic T lymphocytes activation at tumor sites.</description><subject>Adenoviridae - genetics</subject><subject>Adenoviruses</subject><subject>Advertising executives</subject><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biology</subject><subject>Cancer</subject><subject>Cancer treatment</subject><subject>CD8 antigen</subject><subject>Cell activation</subject><subject>Cell Line, Tumor</subject><subject>Cloning</subject><subject>Colorectal cancer</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Gelatinase B</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic Vectors</subject><subject>Immunity</subject><subject>Immunoregulation</subject><subject>Inflammation</subject><subject>Inhibition</subject><subject>Injections, Intralesional</subject><subject>Interleukin 17</subject><subject>Interleukin-17 - antagonists & inhibitors</subject><subject>Interleukin-17 - genetics</subject><subject>Interleukin-17 - immunology</subject><subject>Laboratory animals</subject><subject>Liver cancer</subject><subject>Lung cancer</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Lymphocytes, Tumor-Infiltrating - pathology</subject><subject>Matrix Metalloproteinase 9 - genetics</subject><subject>Matrix Metalloproteinase 9 - immunology</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Melanoma</subject><subject>Melanoma, Experimental - blood supply</subject><subject>Melanoma, Experimental - genetics</subject><subject>Melanoma, Experimental - metabolism</subject><subject>Melanoma, Experimental - pathology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neovascularization, Pathologic</subject><subject>Ovarian cancer</subject><subject>Penicillin</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - genetics</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - immunology</subject><subject>RNA, Small Interfering - genetics</subject><subject>Rodents</subject><subject>siRNA</subject><subject>Skin cancer</subject><subject>Skin Neoplasms - blood supply</subject><subject>Skin Neoplasms - genetics</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - pathology</subject><subject>Splenocytes</subject><subject>Studies</subject><subject>Suppressor cells</subject><subject>Surgery</subject><subject>T cells</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>T-Lymphocytes, Cytotoxic - pathology</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - pathology</subject><subject>Toxicity</subject><subject>Tumor Microenvironment - genetics</subject><subject>Tumor-infiltrating lymphocytes</subject><subject>Tumors</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Vascular Endothelial Growth Factor A - immunology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1uL1DAUx4so7rr6DUQLguhDx6a59kVYFi8DAwveXkOaSTsZ0mRM0mUH_PCmO91hKvsgeUhIfud_cm5Z9hKUCwAp-LB1g7fCLHbOqkVZYgggeJSdgxpWBalK-PjkfJY9C2E7QoyQp9lZBSGtCMbn2Z-l3ehGR-1s7tp8uSoAvcy1zePQO5_3Wnqn7I32zvbKxlwM3biHXO6ji-5WSx33o-UdX2jbahO9iNp2udn3u41LoApHxaJRwo-PSVk9z560wgT1Ytovsp-fP_24-lqsrr8sry5XhaSYxQKhltCG0RpIVitJQItKQDEpKwxxhUrGMGhriIgijEIqRaMABqUo00VDhIAX2euD7s64wKfEBQ5gRVldV4gmYnkg1k5s-c7rXvg9d0LzuwvnOy581NIojkWLZQURRS1FUiAmsGI1SflUhNKmSVofJ29D06u1TOnywsxE5y9Wb3jnbjjEKSZaJ4F3k4B3vwcVIu91kMoYYZUb0r8rBimEmJUJffMP-nB0E9WJFECqkUt-5SjKLxFljEFSjW4XD1BprVUqVuqyVFo1N3g_M0hMVLexE0MIfPn92_-z17_m7NsTdqOEiZvgzDA2aZiD6ACmJg3Bq_aYZFDycUjus8HHIeHTkCSzV6cFOhrdTwX8C84MDTo</recordid><startdate>20130125</startdate><enddate>20130125</enddate><creator>Hayata, Keiji</creator><creator>Iwahashi, Makoto</creator><creator>Ojima, Toshiyasu</creator><creator>Katsuda, Masahiro</creator><creator>Iida, Takeshi</creator><creator>Nakamori, Mikihito</creator><creator>Ueda, Kentaro</creator><creator>Nakamura, Masaki</creator><creator>Miyazawa, Motoki</creator><creator>Tsuji, Toshiaki</creator><creator>Yamaue, Hiroki</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130125</creationdate><title>Inhibition of IL-17A in tumor microenvironment augments cytotoxicity of tumor-infiltrating lymphocytes in tumor-bearing mice</title><author>Hayata, Keiji ; Iwahashi, Makoto ; Ojima, Toshiyasu ; Katsuda, Masahiro ; Iida, Takeshi ; Nakamori, Mikihito ; Ueda, Kentaro ; Nakamura, Masaki ; Miyazawa, Motoki ; Tsuji, Toshiaki ; Yamaue, Hiroki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-44f67b8791c89ec61f401756025352408851f9346e68737cabe1510a06e6b6aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adenoviridae - genetics</topic><topic>Adenoviruses</topic><topic>Advertising executives</topic><topic>Analysis</topic><topic>Angiogenesis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biology</topic><topic>Cancer</topic><topic>Cancer treatment</topic><topic>CD8 antigen</topic><topic>Cell activation</topic><topic>Cell Line, Tumor</topic><topic>Cloning</topic><topic>Colorectal cancer</topic><topic>Cytokines</topic><topic>Cytotoxicity</topic><topic>Gelatinase B</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic Vectors</topic><topic>Immunity</topic><topic>Immunoregulation</topic><topic>Inflammation</topic><topic>Inhibition</topic><topic>Injections, Intralesional</topic><topic>Interleukin 17</topic><topic>Interleukin-17 - antagonists & inhibitors</topic><topic>Interleukin-17 - genetics</topic><topic>Interleukin-17 - immunology</topic><topic>Laboratory animals</topic><topic>Liver cancer</topic><topic>Lung cancer</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Lymphocytes, Tumor-Infiltrating - pathology</topic><topic>Matrix Metalloproteinase 9 - genetics</topic><topic>Matrix Metalloproteinase 9 - immunology</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Melanoma</topic><topic>Melanoma, Experimental - blood supply</topic><topic>Melanoma, Experimental - genetics</topic><topic>Melanoma, Experimental - metabolism</topic><topic>Melanoma, Experimental - pathology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neovascularization, Pathologic</topic><topic>Ovarian cancer</topic><topic>Penicillin</topic><topic>Platelet Endothelial Cell Adhesion Molecule-1 - genetics</topic><topic>Platelet Endothelial Cell Adhesion Molecule-1 - immunology</topic><topic>RNA, Small Interfering - genetics</topic><topic>Rodents</topic><topic>siRNA</topic><topic>Skin cancer</topic><topic>Skin Neoplasms - blood supply</topic><topic>Skin Neoplasms - genetics</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - pathology</topic><topic>Splenocytes</topic><topic>Studies</topic><topic>Suppressor cells</topic><topic>Surgery</topic><topic>T cells</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>T-Lymphocytes, Cytotoxic - pathology</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - pathology</topic><topic>Toxicity</topic><topic>Tumor Microenvironment - genetics</topic><topic>Tumor-infiltrating lymphocytes</topic><topic>Tumors</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><topic>Vascular Endothelial Growth Factor A - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hayata, Keiji</creatorcontrib><creatorcontrib>Iwahashi, Makoto</creatorcontrib><creatorcontrib>Ojima, Toshiyasu</creatorcontrib><creatorcontrib>Katsuda, Masahiro</creatorcontrib><creatorcontrib>Iida, Takeshi</creatorcontrib><creatorcontrib>Nakamori, Mikihito</creatorcontrib><creatorcontrib>Ueda, Kentaro</creatorcontrib><creatorcontrib>Nakamura, Masaki</creatorcontrib><creatorcontrib>Miyazawa, Motoki</creatorcontrib><creatorcontrib>Tsuji, Toshiaki</creatorcontrib><creatorcontrib>Yamaue, Hiroki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hayata, Keiji</au><au>Iwahashi, Makoto</au><au>Ojima, Toshiyasu</au><au>Katsuda, Masahiro</au><au>Iida, Takeshi</au><au>Nakamori, Mikihito</au><au>Ueda, Kentaro</au><au>Nakamura, Masaki</au><au>Miyazawa, Motoki</au><au>Tsuji, Toshiaki</au><au>Yamaue, Hiroki</au><au>Gao, Jian-Xin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of IL-17A in tumor microenvironment augments cytotoxicity of tumor-infiltrating lymphocytes in tumor-bearing mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-01-25</date><risdate>2013</risdate><volume>8</volume><issue>1</issue><spage>e53131</spage><pages>e53131-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>It remains controversial whether IL-17A promotes or inhibits cancer progression. We hypothesized that IL-17A that is locally produced in the tumor microenvironment has an important role in angiogenesis and tumor immunity. We investigated the effect of inhibiting IL-17A at tumor sites on tumor growth and on local and systemic anti-tumor immunity. MC38 or B16 cells were inoculated subcutaneously into mice, and intratumoral injection of an adenovirus vector expressing siRNA against the mouse IL-17A gene (Ad-si-IL-17) significantly inhibited tumor growth in both tumor models compared with control mice. Inhibition of IL-17A at tumor sites significantly suppressed CD31, MMP9, and VEGF expression in tumor tissue. The cytotoxic activity of CD8(+) T cells from tumor-infiltrating lymphocytes in mice treated with Ad-si-IL-17 was significantly higher than in control mice; however, CD8(+) T cells from splenocytes had similar activity levels. Suppression of IL-17A at tumor sites led to a Th1-dominant environment, and moreover, eliminated myeloid-derived suppressor cells and regulatory T cells at tumor sites but not in splenocytes. In conclusion, blockade of IL-17A at tumor sites helped suppress tumor growth by inhibiting angiogenesis as well as cytotoxic T lymphocytes activation at tumor sites.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23372655</pmid><doi>10.1371/journal.pone.0053131</doi><tpages>e53131</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-01, Vol.8 (1), p.e53131 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1327899247 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenoviridae - genetics Adenoviruses Advertising executives Analysis Angiogenesis Animal models Animals Biology Cancer Cancer treatment CD8 antigen Cell activation Cell Line, Tumor Cloning Colorectal cancer Cytokines Cytotoxicity Gelatinase B Gene Expression Regulation, Neoplastic Genetic Vectors Immunity Immunoregulation Inflammation Inhibition Injections, Intralesional Interleukin 17 Interleukin-17 - antagonists & inhibitors Interleukin-17 - genetics Interleukin-17 - immunology Laboratory animals Liver cancer Lung cancer Lymphocytes Lymphocytes T Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - pathology Matrix Metalloproteinase 9 - genetics Matrix Metalloproteinase 9 - immunology Medical research Medicine Melanoma Melanoma, Experimental - blood supply Melanoma, Experimental - genetics Melanoma, Experimental - metabolism Melanoma, Experimental - pathology Mice Mice, Inbred C57BL Neovascularization, Pathologic Ovarian cancer Penicillin Platelet Endothelial Cell Adhesion Molecule-1 - genetics Platelet Endothelial Cell Adhesion Molecule-1 - immunology RNA, Small Interfering - genetics Rodents siRNA Skin cancer Skin Neoplasms - blood supply Skin Neoplasms - genetics Skin Neoplasms - metabolism Skin Neoplasms - pathology Splenocytes Studies Suppressor cells Surgery T cells T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - pathology T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - pathology Toxicity Tumor Microenvironment - genetics Tumor-infiltrating lymphocytes Tumors Vascular endothelial growth factor Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - immunology |
| title | Inhibition of IL-17A in tumor microenvironment augments cytotoxicity of tumor-infiltrating lymphocytes in tumor-bearing mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T17%3A17%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inhibition%20of%20IL-17A%20in%20tumor%20microenvironment%20augments%20cytotoxicity%20of%20tumor-infiltrating%20lymphocytes%20in%20tumor-bearing%20mice&rft.jtitle=PloS%20one&rft.au=Hayata,%20Keiji&rft.date=2013-01-25&rft.volume=8&rft.issue=1&rft.spage=e53131&rft.pages=e53131-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0053131&rft_dat=%3Cgale_plos_%3EA478883629%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1327899247&rft_id=info:pmid/23372655&rft_galeid=A478883629&rft_doaj_id=oai_doaj_org_article_5af5c23474f74ca48a5e896726e677bb&rfr_iscdi=true |