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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)479-490
Number of pages12
JournalJournal of Experimental Medicine
Volume208
Issue number3
DOIs
StatePublished - Mar 14 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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