Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation
The human breast tumor microenvironment can display features of T helper type 2 (Th2) inflammation, and Th2 inflammation can promote tumor development. However, the molecular and cellular mechanisms contributing to Th2 inflammation in breast tumors remain unclear. Here, we show that human breast can...
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| Veröffentlicht in: | The Journal of experimental medicine 2011-03, Vol.208 (3), p.479-490 |
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| container_title | The Journal of experimental medicine |
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| creator | Pedroza-Gonzalez, Alexander Xu, Kangling Wu, Te-Chia Aspord, Caroline Tindle, Sasha Marches, Florentina Gallegos, Michael Burton, Elizabeth C Savino, Daniel Hori, Toshiyuki Tanaka, Yuetsu Zurawski, Sandra Zurawski, Gerard Bover, Laura Liu, Yong-Jun Banchereau, Jacques Palucka, A Karolina |
| description | The human breast tumor microenvironment can display features of T helper type 2 (Th2) inflammation, and Th2 inflammation can promote tumor development. However, the molecular and cellular mechanisms contributing to Th2 inflammation in breast tumors remain unclear. Here, we show that human breast cancer cells produce thymic stromal lymphopoietin (TSLP). Breast tumor supernatants, in a TSLP-dependent manner, induce expression of OX40L on dendritic cells (DCs). OX40L(+) DCs are found in primary breast tumor infiltrates. OX40L(+) DCs drive development of inflammatory Th2 cells producing interleukin-13 and tumor necrosis factor in vitro. Antibodies neutralizing TSLP or OX40L inhibit breast tumor growth and interleukin-13 production in a xenograft model. Thus, breast cancer cell-derived TSLP contributes to the inflammatory Th2 microenvironment conducive to breast tumor development by inducing OX40L expression on DCs. |
| doi_str_mv | 10.1084/jem.20102131 |
| format | Article |
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However, the molecular and cellular mechanisms contributing to Th2 inflammation in breast tumors remain unclear. Here, we show that human breast cancer cells produce thymic stromal lymphopoietin (TSLP). Breast tumor supernatants, in a TSLP-dependent manner, induce expression of OX40L on dendritic cells (DCs). OX40L(+) DCs are found in primary breast tumor infiltrates. OX40L(+) DCs drive development of inflammatory Th2 cells producing interleukin-13 and tumor necrosis factor in vitro. Antibodies neutralizing TSLP or OX40L inhibit breast tumor growth and interleukin-13 production in a xenograft model. Thus, breast cancer cell-derived TSLP contributes to the inflammatory Th2 microenvironment conducive to breast tumor development by inducing OX40L expression on DCs.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20102131</identifier><identifier>PMID: 21339324</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Animals ; Antibodies, Neoplasm - immunology ; Breast Neoplasms - physiopathology ; Cytokines - physiology ; Dendritic Cells - immunology ; Dendritic Cells - physiology ; Female ; Gene Expression Regulation, Neoplastic - physiology ; Humans ; Inflammation - physiopathology ; Lymphocytes, Tumor-Infiltrating - immunology ; Lymphocytes, Tumor-Infiltrating - physiology ; Mice ; Neoplasm Transplantation ; OX40 Ligand - physiology ; Th2 Cells - immunology ; Th2 Cells - physiology</subject><ispartof>The Journal of experimental medicine, 2011-03, Vol.208 (3), p.479-490</ispartof><rights>2011 Pedroza-Gonzalez et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-e2bcbf3fb0a198e8dc3d3ab9132c8257b39e805c19a84d36ef6edda00d539f9c3</citedby><cites>FETCH-LOGICAL-c481t-e2bcbf3fb0a198e8dc3d3ab9132c8257b39e805c19a84d36ef6edda00d539f9c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21339324$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pedroza-Gonzalez, Alexander</creatorcontrib><creatorcontrib>Xu, Kangling</creatorcontrib><creatorcontrib>Wu, Te-Chia</creatorcontrib><creatorcontrib>Aspord, Caroline</creatorcontrib><creatorcontrib>Tindle, Sasha</creatorcontrib><creatorcontrib>Marches, Florentina</creatorcontrib><creatorcontrib>Gallegos, Michael</creatorcontrib><creatorcontrib>Burton, Elizabeth C</creatorcontrib><creatorcontrib>Savino, Daniel</creatorcontrib><creatorcontrib>Hori, Toshiyuki</creatorcontrib><creatorcontrib>Tanaka, Yuetsu</creatorcontrib><creatorcontrib>Zurawski, Sandra</creatorcontrib><creatorcontrib>Zurawski, Gerard</creatorcontrib><creatorcontrib>Bover, Laura</creatorcontrib><creatorcontrib>Liu, Yong-Jun</creatorcontrib><creatorcontrib>Banchereau, Jacques</creatorcontrib><creatorcontrib>Palucka, A Karolina</creatorcontrib><title>Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>The human breast tumor microenvironment can display features of T helper type 2 (Th2) inflammation, and Th2 inflammation can promote tumor development. However, the molecular and cellular mechanisms contributing to Th2 inflammation in breast tumors remain unclear. Here, we show that human breast cancer cells produce thymic stromal lymphopoietin (TSLP). Breast tumor supernatants, in a TSLP-dependent manner, induce expression of OX40L on dendritic cells (DCs). OX40L(+) DCs are found in primary breast tumor infiltrates. OX40L(+) DCs drive development of inflammatory Th2 cells producing interleukin-13 and tumor necrosis factor in vitro. Antibodies neutralizing TSLP or OX40L inhibit breast tumor growth and interleukin-13 production in a xenograft model. Thus, breast cancer cell-derived TSLP contributes to the inflammatory Th2 microenvironment conducive to breast tumor development by inducing OX40L expression on DCs.</description><subject>Animals</subject><subject>Antibodies, Neoplasm - immunology</subject><subject>Breast Neoplasms - physiopathology</subject><subject>Cytokines - physiology</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - physiology</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - physiology</subject><subject>Humans</subject><subject>Inflammation - physiopathology</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Lymphocytes, Tumor-Infiltrating - physiology</subject><subject>Mice</subject><subject>Neoplasm Transplantation</subject><subject>OX40 Ligand - physiology</subject><subject>Th2 Cells - immunology</subject><subject>Th2 Cells - physiology</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkb1v1jAQh60K1L603ZiRNxZSznb8xl6QUEULUiWWdrYc5_LGVRwH26HKf0-qfggmlrvhnvvpTg8h7xlcMFD153sMFxwYcCbYEdkxWUOlpVBvyA6A84oBNCfkXc73AKyu5f6YnGys0ILXO2JuhzV4R3NJMdiRjmuYhzhHj8VPtI-5YMp0WIKdaJvQ5kLLEmKihxQfykDblc7bZtzoAy3rjJRTP_WjDcEWH6cz8ra3Y8bz535K7q6-3V5-r25-Xv-4_HpTuVqxUiFvXduLvgXLtELVOdEJ22omuFNcNq3QqEA6pq2qO7HHfo9dZwE6KXSvnTglX55y56UN2DmcSrKjmZMPNq0mWm_-nUx-MIf42wiQSqr9FvDxOSDFXwvmYoLPDsfRThiXbDQ0TDaNYP8llWy40lvdyE9PpEsx54T96z0MzKM8s8kzL_I2_MPfP7zCL7bEH3dRmNI</recordid><startdate>20110314</startdate><enddate>20110314</enddate><creator>Pedroza-Gonzalez, Alexander</creator><creator>Xu, Kangling</creator><creator>Wu, Te-Chia</creator><creator>Aspord, Caroline</creator><creator>Tindle, Sasha</creator><creator>Marches, Florentina</creator><creator>Gallegos, Michael</creator><creator>Burton, Elizabeth C</creator><creator>Savino, Daniel</creator><creator>Hori, Toshiyuki</creator><creator>Tanaka, Yuetsu</creator><creator>Zurawski, Sandra</creator><creator>Zurawski, Gerard</creator><creator>Bover, Laura</creator><creator>Liu, Yong-Jun</creator><creator>Banchereau, Jacques</creator><creator>Palucka, A Karolina</creator><general>The Rockefeller University Press</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>7X8</scope><scope>7T5</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20110314</creationdate><title>Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation</title><author>Pedroza-Gonzalez, Alexander ; 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| subjects | Animals Antibodies, Neoplasm - immunology Breast Neoplasms - physiopathology Cytokines - physiology Dendritic Cells - immunology Dendritic Cells - physiology Female Gene Expression Regulation, Neoplastic - physiology Humans Inflammation - physiopathology Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - physiology Mice Neoplasm Transplantation OX40 Ligand - physiology Th2 Cells - immunology Th2 Cells - physiology |
| title | Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation |
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