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Fibroblasts and macrophages cooperate to create a pro-tumorigenic and immune resistant environment via activation of TGF-β/IL-6 pathway in neuroblastoma by Kevin Louault; Tania Porras; Meng-Hua Lee; Sakunthala Muthugounder; Rebekah J. Kennedy; Laurence Blavier; Emily Sarte; G. Esteban Fernandez; Fusheng Yang; Bruce R. Pawel; Hiroyuki Shimada; Shahab Asgharzadeh; Yves A. DeClerck is a Immunology and Microbiology article available to read on EtoBox.

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## ABSTRACT Tumor-associated macrophages (TAM) and cancer-associated fibroblasts (CAF) and their precursor mesenchymal stromal cells (MSC) are often detected together in tumors, but how they cooperate is not well understood. Here, we show that TAM and CAF are the most abundant nonmalignant cells and are present together in untreated human neuroblastoma (NB) tumors that are also poorly infiltrated with T and natural killer (NK) cells. We then show that MSC and CAF-MSC harvested from NB tumors protected human monocytes (MN) from spontaneous apoptosis in an interleukin (IL)-6 dependent mechanism. The interactions of MN and MSC with NB cells resulted in a significant induction or increase in the expression of several pro-tumorigenic cytokines/chemokines (TGF-β1, MCP-1, IL-6, IL-8, and IL-4) but not of anti-tumorigenic cytokines (TNF-α, IL-12) by MN or MSC, while also inducing cytokine expression in quiescent NB cells. We then identified a TGF-β1/IL-6 pathway where TGF-β1 stimulated the expression of IL-6 in NB cells and MSC, promoting TAM survival. Evidence for the contribution of TAM and MSC to the activation of this pathway was then provided in xenotransplanted NB tumors and patients

Who reads Fibroblasts and macrophages cooperate to create a pro-tumorigenic and immune resistant environment via activation of TGF-β/IL-6 pathway in neuroblastoma?

Author

Kevin Louault; Tania Porras; Meng-Hua Lee; Sakunthala Muthugounder; Rebekah J. Kennedy; Laurence Blavier; Emily Sarte; G. Esteban Fernandez; Fusheng Yang; Bruce R. Pawel; Hiroyuki Shimada; Shahab Asgharzadeh; Yves A. DeClerck

Published

2022

Language

EN

Field

Immunology and Microbiology (Life Sciences)