title: 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.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pedroza-Gonzalez
authors.forename: Kangling
authors.initials: K
authors.lastname: Xu
authors.forename: Te-Chia
authors.initials: TC
authors.lastname: Wu
authors.forename: Caroline
authors.initials: C
authors.lastname: Aspord
authors.forename: Sasha
authors.initials: S
authors.lastname: Tindle
authors.forename: Florentina
authors.initials: F
authors.lastname: Marches
authors.forename: Michael
authors.initials: M
authors.lastname: Gallegos
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Burton
authors.forename: Daniel
authors.initials: D
authors.lastname: Savino
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hori
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Sandra
authors.initials: S
authors.lastname: Zurawski
authors.forename: Gerard
authors.initials: G
authors.lastname: Zurawski
authors.forename: Laura
authors.initials: L
authors.lastname: Bover
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: A Karolina
authors.initials: AK
authors.lastname: Palucka
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D001943:Breast Neoplasms / Q000503:physiopathology*; D016207:Cytokines / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000502:physiology; D051379:Mice; D009368:Neoplasm Transplantation; D053278:OX40 Ligand / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology / Q000502:physiology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000912:Antibodies, Neoplasm; D016207:Cytokines; D053278:OX40 Ligand; C089251:TNFSF4 protein, human; D000094632:Thymic Stromal Lymphopoietin