IL-13 receptors as possible therapeutic targets in diffuse intrinsic pontine glioma
Diffuse intrinsic pontine glioma (DIPG) is a universally fatal childhood cancer of the brain. Despite the introduction of conventional chemotherapy and radiotherapy, improvements in survival have been marginal and long-term survivorship is uncommon. Thus, new targets for therapeutics are critically...
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| Veröffentlicht in: | PloS one 2018-04, Vol.13 (4), p.e0193565-e0193565 |
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| creator | Berlow, Noah E Svalina, Matthew N Quist, Michael J Settelmeyer, Teagan P Zherebitskiy, Viktor Kogiso, Mari Qi, Lin Du, Yuchen Hawkins, Cynthia E Hulleman, Esther Li, Xiao-Nan Gultekin, Sakir H Keller, Charles |
| description | Diffuse intrinsic pontine glioma (DIPG) is a universally fatal childhood cancer of the brain. Despite the introduction of conventional chemotherapy and radiotherapy, improvements in survival have been marginal and long-term survivorship is uncommon. Thus, new targets for therapeutics are critically needed. Early phase clinical trials exploring molecularly-targeted therapies against the epidermal growth factor receptor (EGFR) and novel immunotherapies targeting interleukin receptor-13α2 (IL-13Rα2) have demonstrated activity in this disease. To identify additional therapeutic markers for cell surface receptors, we performed exome sequencing (16 new samples, 22 previously published samples, total 38 with 26 matched normal DNA samples), RNA deep sequencing (17 new samples, 11 previously published samples, total 28 with 18 matched normal RNA samples), and immunohistochemistry (17 DIPG tissue samples) to examine the expression of the interleukin-4 (IL-4) signaling axis components (IL-4, interleukin 13 (IL-13), and their respective receptors IL-4Rα, IL-13Rα1, and IL-13Rα2). In addition, we correlated cytokine and receptor expression with expression of the oncogenes EGFR and c-MET. In DIPG tissues, transcript-level analysis found significant expression of IL-4, IL-13, and IL-13Rα1/2, with strong differential expression of IL-13Rα1/2 in tumor versus normal brain. At the protein level, immunohistochemical studies revealed high content of IL-4 and IL-13Rα1/2 but notably low expression of IL-13. Additionally, a strong positive correlation was observed between c-Met and IL-4Rα. The genomic and transcriptional landscape across all samples was also summarized. These data create a foundation for the design of potential new immunotherapies targeting IL-13 cell surface receptors in DIPG. |
| doi_str_mv | 10.1371/journal.pone.0193565 |
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Despite the introduction of conventional chemotherapy and radiotherapy, improvements in survival have been marginal and long-term survivorship is uncommon. Thus, new targets for therapeutics are critically needed. Early phase clinical trials exploring molecularly-targeted therapies against the epidermal growth factor receptor (EGFR) and novel immunotherapies targeting interleukin receptor-13α2 (IL-13Rα2) have demonstrated activity in this disease. To identify additional therapeutic markers for cell surface receptors, we performed exome sequencing (16 new samples, 22 previously published samples, total 38 with 26 matched normal DNA samples), RNA deep sequencing (17 new samples, 11 previously published samples, total 28 with 18 matched normal RNA samples), and immunohistochemistry (17 DIPG tissue samples) to examine the expression of the interleukin-4 (IL-4) signaling axis components (IL-4, interleukin 13 (IL-13), and their respective receptors IL-4Rα, IL-13Rα1, and IL-13Rα2). In addition, we correlated cytokine and receptor expression with expression of the oncogenes EGFR and c-MET. In DIPG tissues, transcript-level analysis found significant expression of IL-4, IL-13, and IL-13Rα1/2, with strong differential expression of IL-13Rα1/2 in tumor versus normal brain. At the protein level, immunohistochemical studies revealed high content of IL-4 and IL-13Rα1/2 but notably low expression of IL-13. Additionally, a strong positive correlation was observed between c-Met and IL-4Rα. The genomic and transcriptional landscape across all samples was also summarized. These data create a foundation for the design of potential new immunotherapies targeting IL-13 cell surface receptors in DIPG.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0193565</identifier><identifier>PMID: 29621254</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Biology and life sciences ; Brain ; Brain cancer ; Brain research ; Brain tumors ; c-Met protein ; Cancer ; Cancer therapies ; Cell surface ; Chemotherapy ; Children ; Children & youth ; Clinical trials ; Cytokines ; Deoxyribonucleic acid ; DNA ; DNA sequencing ; Epidermal growth factor ; Epidermal growth factor receptors ; Gene expression ; Gene sequencing ; Genomes ; Glioma ; Gliomas ; Immunohistochemistry ; Immunotherapy ; Interleukin 13 ; Interleukin 4 ; Kinases ; Medical prognosis ; Medical research ; Medicine and Health Sciences ; Pathology ; Patient outcomes ; Patients ; Pediatrics ; Radiation therapy ; Receptors ; Research and Analysis Methods ; Ribonucleic acid ; RNA ; RNA sequencing ; Signaling ; Survival ; Therapeutic applications ; Transcription ; Tumors</subject><ispartof>PloS one, 2018-04, Vol.13 (4), p.e0193565-e0193565</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Berlow et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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>2018 Berlow et al 2018 Berlow et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c653t-5e2d5d37d03f85161234216a3e0611679c3ff502b22fc91afce2a71e1f993eb43</citedby><cites>FETCH-LOGICAL-c653t-5e2d5d37d03f85161234216a3e0611679c3ff502b22fc91afce2a71e1f993eb43</cites><orcidid>0000-0001-8666-3152 ; 0000-0002-4717-0408 ; 0000-0001-9256-947X ; 0000-0003-2505-7487</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886401/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886401/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29621254$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Berlow, Noah E</creatorcontrib><creatorcontrib>Svalina, Matthew N</creatorcontrib><creatorcontrib>Quist, Michael J</creatorcontrib><creatorcontrib>Settelmeyer, Teagan P</creatorcontrib><creatorcontrib>Zherebitskiy, Viktor</creatorcontrib><creatorcontrib>Kogiso, Mari</creatorcontrib><creatorcontrib>Qi, Lin</creatorcontrib><creatorcontrib>Du, Yuchen</creatorcontrib><creatorcontrib>Hawkins, Cynthia E</creatorcontrib><creatorcontrib>Hulleman, Esther</creatorcontrib><creatorcontrib>Li, Xiao-Nan</creatorcontrib><creatorcontrib>Gultekin, Sakir H</creatorcontrib><creatorcontrib>Keller, Charles</creatorcontrib><title>IL-13 receptors as possible therapeutic targets in diffuse intrinsic pontine glioma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Diffuse intrinsic pontine glioma (DIPG) is a universally fatal childhood cancer of the brain. Despite the introduction of conventional chemotherapy and radiotherapy, improvements in survival have been marginal and long-term survivorship is uncommon. Thus, new targets for therapeutics are critically needed. Early phase clinical trials exploring molecularly-targeted therapies against the epidermal growth factor receptor (EGFR) and novel immunotherapies targeting interleukin receptor-13α2 (IL-13Rα2) have demonstrated activity in this disease. To identify additional therapeutic markers for cell surface receptors, we performed exome sequencing (16 new samples, 22 previously published samples, total 38 with 26 matched normal DNA samples), RNA deep sequencing (17 new samples, 11 previously published samples, total 28 with 18 matched normal RNA samples), and immunohistochemistry (17 DIPG tissue samples) to examine the expression of the interleukin-4 (IL-4) signaling axis components (IL-4, interleukin 13 (IL-13), and their respective receptors IL-4Rα, IL-13Rα1, and IL-13Rα2). In addition, we correlated cytokine and receptor expression with expression of the oncogenes EGFR and c-MET. In DIPG tissues, transcript-level analysis found significant expression of IL-4, IL-13, and IL-13Rα1/2, with strong differential expression of IL-13Rα1/2 in tumor versus normal brain. At the protein level, immunohistochemical studies revealed high content of IL-4 and IL-13Rα1/2 but notably low expression of IL-13. Additionally, a strong positive correlation was observed between c-Met and IL-4Rα. The genomic and transcriptional landscape across all samples was also summarized. These data create a foundation for the design of potential new immunotherapies targeting IL-13 cell surface receptors in DIPG.</description><subject>Analysis</subject><subject>Biology and life sciences</subject><subject>Brain</subject><subject>Brain cancer</subject><subject>Brain research</subject><subject>Brain tumors</subject><subject>c-Met protein</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell surface</subject><subject>Chemotherapy</subject><subject>Children</subject><subject>Children & youth</subject><subject>Clinical trials</subject><subject>Cytokines</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA sequencing</subject><subject>Epidermal growth factor</subject><subject>Epidermal growth factor receptors</subject><subject>Gene expression</subject><subject>Gene sequencing</subject><subject>Genomes</subject><subject>Glioma</subject><subject>Gliomas</subject><subject>Immunohistochemistry</subject><subject>Immunotherapy</subject><subject>Interleukin 13</subject><subject>Interleukin 4</subject><subject>Kinases</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Pathology</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Radiation therapy</subject><subject>Receptors</subject><subject>Research and Analysis Methods</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA sequencing</subject><subject>Signaling</subject><subject>Survival</subject><subject>Therapeutic 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receptors as possible therapeutic targets in diffuse intrinsic pontine glioma</title><author>Berlow, Noah E ; Svalina, Matthew N ; Quist, Michael J ; Settelmeyer, Teagan P ; Zherebitskiy, Viktor ; Kogiso, Mari ; Qi, Lin ; Du, Yuchen ; Hawkins, Cynthia E ; Hulleman, Esther ; Li, Xiao-Nan ; Gultekin, Sakir H ; Keller, Charles</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c653t-5e2d5d37d03f85161234216a3e0611679c3ff502b22fc91afce2a71e1f993eb43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Analysis</topic><topic>Biology and life sciences</topic><topic>Brain</topic><topic>Brain cancer</topic><topic>Brain research</topic><topic>Brain tumors</topic><topic>c-Met protein</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Cell surface</topic><topic>Chemotherapy</topic><topic>Children</topic><topic>Children & youth</topic><topic>Clinical 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One</addtitle><date>2018-04-05</date><risdate>2018</risdate><volume>13</volume><issue>4</issue><spage>e0193565</spage><epage>e0193565</epage><pages>e0193565-e0193565</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Diffuse intrinsic pontine glioma (DIPG) is a universally fatal childhood cancer of the brain. Despite the introduction of conventional chemotherapy and radiotherapy, improvements in survival have been marginal and long-term survivorship is uncommon. Thus, new targets for therapeutics are critically needed. Early phase clinical trials exploring molecularly-targeted therapies against the epidermal growth factor receptor (EGFR) and novel immunotherapies targeting interleukin receptor-13α2 (IL-13Rα2) have demonstrated activity in this disease. To identify additional therapeutic markers for cell surface receptors, we performed exome sequencing (16 new samples, 22 previously published samples, total 38 with 26 matched normal DNA samples), RNA deep sequencing (17 new samples, 11 previously published samples, total 28 with 18 matched normal RNA samples), and immunohistochemistry (17 DIPG tissue samples) to examine the expression of the interleukin-4 (IL-4) signaling axis components (IL-4, interleukin 13 (IL-13), and their respective receptors IL-4Rα, IL-13Rα1, and IL-13Rα2). In addition, we correlated cytokine and receptor expression with expression of the oncogenes EGFR and c-MET. In DIPG tissues, transcript-level analysis found significant expression of IL-4, IL-13, and IL-13Rα1/2, with strong differential expression of IL-13Rα1/2 in tumor versus normal brain. At the protein level, immunohistochemical studies revealed high content of IL-4 and IL-13Rα1/2 but notably low expression of IL-13. Additionally, a strong positive correlation was observed between c-Met and IL-4Rα. The genomic and transcriptional landscape across all samples was also summarized. These data create a foundation for the design of potential new immunotherapies targeting IL-13 cell surface receptors in DIPG.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29621254</pmid><doi>10.1371/journal.pone.0193565</doi><tpages>e0193565</tpages><orcidid>https://orcid.org/0000-0001-8666-3152</orcidid><orcidid>https://orcid.org/0000-0002-4717-0408</orcidid><orcidid>https://orcid.org/0000-0001-9256-947X</orcidid><orcidid>https://orcid.org/0000-0003-2505-7487</orcidid><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_2022120558 |
| source | DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Analysis Biology and life sciences Brain Brain cancer Brain research Brain tumors c-Met protein Cancer Cancer therapies Cell surface Chemotherapy Children Children & youth Clinical trials Cytokines Deoxyribonucleic acid DNA DNA sequencing Epidermal growth factor Epidermal growth factor receptors Gene expression Gene sequencing Genomes Glioma Gliomas Immunohistochemistry Immunotherapy Interleukin 13 Interleukin 4 Kinases Medical prognosis Medical research Medicine and Health Sciences Pathology Patient outcomes Patients Pediatrics Radiation therapy Receptors Research and Analysis Methods Ribonucleic acid RNA RNA sequencing Signaling Survival Therapeutic applications Transcription Tumors |
| title | IL-13 receptors as possible therapeutic targets in diffuse intrinsic pontine glioma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T05%3A59%3A24IST&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=IL-13%20receptors%20as%20possible%20therapeutic%20targets%20in%20diffuse%20intrinsic%20pontine%20glioma&rft.jtitle=PloS%20one&rft.au=Berlow,%20Noah%20E&rft.date=2018-04-05&rft.volume=13&rft.issue=4&rft.spage=e0193565&rft.epage=e0193565&rft.pages=e0193565-e0193565&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0193565&rft_dat=%3Cgale_plos_%3EA533497505%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=2022120558&rft_id=info:pmid/29621254&rft_galeid=A533497505&rft_doaj_id=oai_doaj_org_article_e0b9df0d759c44b28069717058dcfed6&rfr_iscdi=true |