TY - JOUR
T1 - Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation
AU - Pedroza-Gonzalez, Alexander
AU - Xu, Kangling
AU - Wu, Te Chia
AU - Aspord, Caroline
AU - Tindle, Sasha
AU - Marches, Florentina
AU - Gallegos, Michael
AU - Burton, Elizabeth C.
AU - Savino, Daniel
AU - Hori, Toshiyuki
AU - Tanaka, Yuetsu
AU - Zurawski, Sandra
AU - Zurawski, Gerard
AU - Bover, Laura
AU - Liu, Yong Jun
AU - Banchereau, Jacques
AU - Palucka, A. Karolina
PY - 2011/3/14
Y1 - 2011/3/14
N2 - 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.
AB - 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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U2 - 10.1084/jem.20102131
DO - 10.1084/jem.20102131
M3 - Article
C2 - 21339324
AN - SCOPUS:79952721606
SN - 0022-1007
VL - 208
SP - 479
EP - 490
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 3
ER -