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J Exp Med. 2011 Mar 14;208(3):479-90. doi: 10.1084/jem.20102131. Epub 2011 Feb 21.

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

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  • 1Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204, USA.

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.

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PMID:
21339324
[PubMed - indexed for MEDLINE]
PMCID:
PMC3058586
Free PMC Article

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