Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation.

Abstract

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.

• Authors: Alexander Pedroza-Gonzalez, Kangling Xu, Te-Chia Wu, Caroline Aspord, Sasha Tindle, Florentina Marches, Michael Gallegos, Elizabeth C Burton, Daniel Savino, Toshiyuki Hori, Yuetsu Tanaka, Sandra Zurawski, Gerard Zurawski, Laura Bover, Yong-Jun Liu, Jacques Banchereau, A Karolina Palucka
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 208 Issue 3 Pg. 479-90 (Mar 14 2011) ISSN: 1540-9538 [Electronic] United States
• PMID: 21339324 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neoplasm
• Cytokines
• OX40 Ligand
• TNFSF4 protein, human
• Thymic Stromal Lymphopoietin

Topics

• Animals
• Antibodies, Neoplasm (immunology)
• Breast Neoplasms (physiopathology)
• Cytokines (physiology)
• Dendritic Cells (immunology, physiology)
• Female
• Gene Expression Regulation, Neoplastic (physiology)
• Humans
• Inflammation (physiopathology)
• Lymphocytes, Tumor-Infiltrating (immunology, physiology)
• Mice
• Neoplasm Transplantation
• OX40 Ligand (physiology)
• Th2 Cells (immunology, physiology)
• Thymic Stromal Lymphopoietin