IL1 Receptor Antagonist Controls Transcriptional Signature of Inflammation in Patients with Metastatic Breast Cancer
Inflammation affects tumor immune surveillance and resistance to therapy. Here, we show that production of IL1β in primary breast cancer tumors is linked with advanced disease and originates from tumor-infiltrating CD11c myeloid cells. IL1β production is triggered by cancer cell membrane-derived TGF...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2018-09, Vol.78 (18), p.5243-5258 |
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| creator | Wu, Te-Chia Xu, Kangling Martinek, Jan Young, Robyn R Banchereau, Romain George, Joshy Turner, Jacob Kim, Kyung In Zurawski, Sandra Wang, Xuan Blankenship, Derek Brookes, Hannah M Marches, Florentina Obermoser, Gerlinde Lavecchio, Elizabeth Levin, Maren K Bae, Sookyoung Chung, Cheng-Han Smith, Jennifer L Cepika, Alma-Martina Oxley, Kyp L Snipes, George J Banchereau, Jacques Pascual, Virginia O'Shaughnessy, Joyce Palucka, A Karolina |
| description | Inflammation affects tumor immune surveillance and resistance to therapy. Here, we show that production of IL1β in primary breast cancer tumors is linked with advanced disease and originates from tumor-infiltrating CD11c
myeloid cells. IL1β production is triggered by cancer cell membrane-derived TGFβ. Neutralizing TGFβ or IL1 receptor prevents breast cancer progression in humanized mouse model. Patients with metastatic HER2
breast cancer display a transcriptional signature of inflammation in the blood leukocytes, which is attenuated after IL1 blockade. When present in primary breast cancer tumors, this signature discriminates patients with poor clinical outcomes in two independent public datasets (TCGA and METABRIC).
IL1β orchestrates tumor-promoting inflammation in breast cancer and can be targeted in patients using an IL1 receptor antagonist.
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| doi_str_mv | 10.1158/0008-5472.CAN-18-0413 |
| format | Article |
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myeloid cells. IL1β production is triggered by cancer cell membrane-derived TGFβ. Neutralizing TGFβ or IL1 receptor prevents breast cancer progression in humanized mouse model. Patients with metastatic HER2
breast cancer display a transcriptional signature of inflammation in the blood leukocytes, which is attenuated after IL1 blockade. When present in primary breast cancer tumors, this signature discriminates patients with poor clinical outcomes in two independent public datasets (TCGA and METABRIC).
IL1β orchestrates tumor-promoting inflammation in breast cancer and can be targeted in patients using an IL1 receptor antagonist.
.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-18-0413</identifier><identifier>PMID: 30012670</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Capecitabine - administration & dosage ; CD11c Antigen - metabolism ; Cell Line, Tumor ; Cell Membrane - metabolism ; Female ; Furans - administration & dosage ; Gene Expression Regulation, Neoplastic ; Humans ; Inflammation ; Interleukin 1 Receptor Antagonist Protein - administration & dosage ; Interleukin 1 Receptor Antagonist Protein - metabolism ; Interleukin-1beta - metabolism ; Ketones - administration & dosage ; Leukocytes, Mononuclear - cytology ; Macrophages - metabolism ; Mice ; Mice, SCID ; Myeloid Cells - metabolism ; Neoplasm Metastasis ; Neoplasm Transplantation ; Paclitaxel - administration & dosage ; Pilot Projects ; Transcription, Genetic ; Transforming Growth Factor beta - metabolism</subject><ispartof>Cancer research (Chicago, Ill.), 2018-09, Vol.78 (18), p.5243-5258</ispartof><rights>2018 American Association for Cancer Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-44dd2b124f0d0967995796d6f2fd893c9f2653a373d510652e6f9f12f530c78f3</citedby><cites>FETCH-LOGICAL-c463t-44dd2b124f0d0967995796d6f2fd893c9f2653a373d510652e6f9f12f530c78f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30012670$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Te-Chia</creatorcontrib><creatorcontrib>Xu, Kangling</creatorcontrib><creatorcontrib>Martinek, Jan</creatorcontrib><creatorcontrib>Young, Robyn R</creatorcontrib><creatorcontrib>Banchereau, Romain</creatorcontrib><creatorcontrib>George, Joshy</creatorcontrib><creatorcontrib>Turner, Jacob</creatorcontrib><creatorcontrib>Kim, Kyung In</creatorcontrib><creatorcontrib>Zurawski, Sandra</creatorcontrib><creatorcontrib>Wang, Xuan</creatorcontrib><creatorcontrib>Blankenship, Derek</creatorcontrib><creatorcontrib>Brookes, Hannah M</creatorcontrib><creatorcontrib>Marches, Florentina</creatorcontrib><creatorcontrib>Obermoser, Gerlinde</creatorcontrib><creatorcontrib>Lavecchio, Elizabeth</creatorcontrib><creatorcontrib>Levin, Maren K</creatorcontrib><creatorcontrib>Bae, Sookyoung</creatorcontrib><creatorcontrib>Chung, Cheng-Han</creatorcontrib><creatorcontrib>Smith, Jennifer L</creatorcontrib><creatorcontrib>Cepika, Alma-Martina</creatorcontrib><creatorcontrib>Oxley, Kyp L</creatorcontrib><creatorcontrib>Snipes, George J</creatorcontrib><creatorcontrib>Banchereau, Jacques</creatorcontrib><creatorcontrib>Pascual, Virginia</creatorcontrib><creatorcontrib>O'Shaughnessy, Joyce</creatorcontrib><creatorcontrib>Palucka, A Karolina</creatorcontrib><title>IL1 Receptor Antagonist Controls Transcriptional Signature of Inflammation in Patients with Metastatic Breast Cancer</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>Inflammation affects tumor immune surveillance and resistance to therapy. Here, we show that production of IL1β in primary breast cancer tumors is linked with advanced disease and originates from tumor-infiltrating CD11c
myeloid cells. IL1β production is triggered by cancer cell membrane-derived TGFβ. Neutralizing TGFβ or IL1 receptor prevents breast cancer progression in humanized mouse model. Patients with metastatic HER2
breast cancer display a transcriptional signature of inflammation in the blood leukocytes, which is attenuated after IL1 blockade. When present in primary breast cancer tumors, this signature discriminates patients with poor clinical outcomes in two independent public datasets (TCGA and METABRIC).
IL1β orchestrates tumor-promoting inflammation in breast cancer and can be targeted in patients using an IL1 receptor antagonist.
.</description><subject>Animals</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>Capecitabine - administration & dosage</subject><subject>CD11c Antigen - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Membrane - metabolism</subject><subject>Female</subject><subject>Furans - administration & dosage</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Interleukin 1 Receptor Antagonist Protein - administration & dosage</subject><subject>Interleukin 1 Receptor Antagonist Protein - metabolism</subject><subject>Interleukin-1beta - metabolism</subject><subject>Ketones - administration & dosage</subject><subject>Leukocytes, Mononuclear - cytology</subject><subject>Macrophages - metabolism</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Myeloid Cells - metabolism</subject><subject>Neoplasm Metastasis</subject><subject>Neoplasm Transplantation</subject><subject>Paclitaxel - administration & dosage</subject><subject>Pilot Projects</subject><subject>Transcription, Genetic</subject><subject>Transforming Growth Factor beta - metabolism</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1PGzEQhq2qqATan9DKx14W_LG215dKIaIQKUDV0rNlvHZwtWsH2wHx7-sVIYLTeGbeeWesB4CvGJ1gzLpThFDXsFaQk8X8usFdg1pMP4AZZrRrRNuyj2C21xyCo5z_1ZRhxD6BQ4oQJlygGSjLFYa_rbGbEhOch6LXMfhc4CKGkuKQ4W3SIZvkN8XHoAf4x6-DLttkYXRwGdygx1FPPegD_FVfNpQMn3y5h1e26FxqycCzZPXkqoOx6TM4cHrI9ssuHoO_P89vF5fN6uZiuZivGtNyWpq27Xtyh0nrUI8kF1IyIXnPHXF9J6mRjnBGNRW0r__ijFjupMPEMYqM6Bw9Bj9efDfbu9H2pl6W9KA2yY86PauovXrfCf5ereOj4lTiTpJq8H1nkOLD1uaiRp-NHQYdbNxmRZDATOCOyyplL1KTYs7Juv0ajNRETE001ERDVWIK10IlVue-vb1xP_WKiP4HpxiT1A</recordid><startdate>20180915</startdate><enddate>20180915</enddate><creator>Wu, Te-Chia</creator><creator>Xu, Kangling</creator><creator>Martinek, Jan</creator><creator>Young, Robyn R</creator><creator>Banchereau, Romain</creator><creator>George, Joshy</creator><creator>Turner, Jacob</creator><creator>Kim, Kyung In</creator><creator>Zurawski, Sandra</creator><creator>Wang, Xuan</creator><creator>Blankenship, Derek</creator><creator>Brookes, Hannah M</creator><creator>Marches, Florentina</creator><creator>Obermoser, Gerlinde</creator><creator>Lavecchio, Elizabeth</creator><creator>Levin, Maren K</creator><creator>Bae, Sookyoung</creator><creator>Chung, Cheng-Han</creator><creator>Smith, Jennifer L</creator><creator>Cepika, Alma-Martina</creator><creator>Oxley, Kyp L</creator><creator>Snipes, George J</creator><creator>Banchereau, Jacques</creator><creator>Pascual, Virginia</creator><creator>O'Shaughnessy, Joyce</creator><creator>Palucka, A Karolina</creator><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180915</creationdate><title>IL1 Receptor Antagonist Controls Transcriptional Signature of Inflammation in Patients with Metastatic Breast Cancer</title><author>Wu, Te-Chia ; Xu, Kangling ; Martinek, Jan ; Young, Robyn R ; Banchereau, Romain ; George, Joshy ; Turner, Jacob ; Kim, Kyung In ; Zurawski, Sandra ; Wang, Xuan ; Blankenship, Derek ; Brookes, Hannah M ; Marches, Florentina ; Obermoser, Gerlinde ; Lavecchio, Elizabeth ; Levin, Maren K ; Bae, Sookyoung ; Chung, Cheng-Han ; Smith, Jennifer L ; Cepika, Alma-Martina ; Oxley, Kyp L ; Snipes, George J ; Banchereau, Jacques ; Pascual, Virginia ; O'Shaughnessy, Joyce ; Palucka, A Karolina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-44dd2b124f0d0967995796d6f2fd893c9f2653a373d510652e6f9f12f530c78f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - metabolism</topic><topic>Capecitabine - administration & dosage</topic><topic>CD11c Antigen - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Membrane - metabolism</topic><topic>Female</topic><topic>Furans - administration & dosage</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Interleukin 1 Receptor Antagonist Protein - administration & dosage</topic><topic>Interleukin 1 Receptor Antagonist Protein - metabolism</topic><topic>Interleukin-1beta - metabolism</topic><topic>Ketones - administration & dosage</topic><topic>Leukocytes, Mononuclear - cytology</topic><topic>Macrophages - metabolism</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Myeloid Cells - metabolism</topic><topic>Neoplasm Metastasis</topic><topic>Neoplasm Transplantation</topic><topic>Paclitaxel - administration & dosage</topic><topic>Pilot Projects</topic><topic>Transcription, Genetic</topic><topic>Transforming Growth Factor beta - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Te-Chia</creatorcontrib><creatorcontrib>Xu, Kangling</creatorcontrib><creatorcontrib>Martinek, Jan</creatorcontrib><creatorcontrib>Young, Robyn R</creatorcontrib><creatorcontrib>Banchereau, Romain</creatorcontrib><creatorcontrib>George, Joshy</creatorcontrib><creatorcontrib>Turner, Jacob</creatorcontrib><creatorcontrib>Kim, Kyung In</creatorcontrib><creatorcontrib>Zurawski, Sandra</creatorcontrib><creatorcontrib>Wang, Xuan</creatorcontrib><creatorcontrib>Blankenship, Derek</creatorcontrib><creatorcontrib>Brookes, Hannah M</creatorcontrib><creatorcontrib>Marches, Florentina</creatorcontrib><creatorcontrib>Obermoser, Gerlinde</creatorcontrib><creatorcontrib>Lavecchio, Elizabeth</creatorcontrib><creatorcontrib>Levin, Maren K</creatorcontrib><creatorcontrib>Bae, Sookyoung</creatorcontrib><creatorcontrib>Chung, Cheng-Han</creatorcontrib><creatorcontrib>Smith, Jennifer L</creatorcontrib><creatorcontrib>Cepika, Alma-Martina</creatorcontrib><creatorcontrib>Oxley, Kyp L</creatorcontrib><creatorcontrib>Snipes, George J</creatorcontrib><creatorcontrib>Banchereau, Jacques</creatorcontrib><creatorcontrib>Pascual, Virginia</creatorcontrib><creatorcontrib>O'Shaughnessy, Joyce</creatorcontrib><creatorcontrib>Palucka, A Karolina</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Te-Chia</au><au>Xu, Kangling</au><au>Martinek, Jan</au><au>Young, Robyn R</au><au>Banchereau, Romain</au><au>George, Joshy</au><au>Turner, Jacob</au><au>Kim, Kyung In</au><au>Zurawski, Sandra</au><au>Wang, Xuan</au><au>Blankenship, Derek</au><au>Brookes, Hannah M</au><au>Marches, Florentina</au><au>Obermoser, Gerlinde</au><au>Lavecchio, Elizabeth</au><au>Levin, Maren K</au><au>Bae, Sookyoung</au><au>Chung, Cheng-Han</au><au>Smith, Jennifer L</au><au>Cepika, Alma-Martina</au><au>Oxley, Kyp L</au><au>Snipes, George J</au><au>Banchereau, Jacques</au><au>Pascual, Virginia</au><au>O'Shaughnessy, Joyce</au><au>Palucka, A Karolina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL1 Receptor Antagonist Controls Transcriptional Signature of Inflammation in Patients with Metastatic Breast Cancer</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2018-09-15</date><risdate>2018</risdate><volume>78</volume><issue>18</issue><spage>5243</spage><epage>5258</epage><pages>5243-5258</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><abstract>Inflammation affects tumor immune surveillance and resistance to therapy. Here, we show that production of IL1β in primary breast cancer tumors is linked with advanced disease and originates from tumor-infiltrating CD11c
myeloid cells. IL1β production is triggered by cancer cell membrane-derived TGFβ. Neutralizing TGFβ or IL1 receptor prevents breast cancer progression in humanized mouse model. Patients with metastatic HER2
breast cancer display a transcriptional signature of inflammation in the blood leukocytes, which is attenuated after IL1 blockade. When present in primary breast cancer tumors, this signature discriminates patients with poor clinical outcomes in two independent public datasets (TCGA and METABRIC).
IL1β orchestrates tumor-promoting inflammation in breast cancer and can be targeted in patients using an IL1 receptor antagonist.
.</abstract><cop>United States</cop><pmid>30012670</pmid><doi>10.1158/0008-5472.CAN-18-0413</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Breast Neoplasms - drug therapy Breast Neoplasms - metabolism Capecitabine - administration & dosage CD11c Antigen - metabolism Cell Line, Tumor Cell Membrane - metabolism Female Furans - administration & dosage Gene Expression Regulation, Neoplastic Humans Inflammation Interleukin 1 Receptor Antagonist Protein - administration & dosage Interleukin 1 Receptor Antagonist Protein - metabolism Interleukin-1beta - metabolism Ketones - administration & dosage Leukocytes, Mononuclear - cytology Macrophages - metabolism Mice Mice, SCID Myeloid Cells - metabolism Neoplasm Metastasis Neoplasm Transplantation Paclitaxel - administration & dosage Pilot Projects Transcription, Genetic Transforming Growth Factor beta - metabolism |
| title | IL1 Receptor Antagonist Controls Transcriptional Signature of Inflammation in Patients with Metastatic Breast Cancer |
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