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Tumor rejection by modulation of tumor stromal fibroblasts

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Item Type:Article
Title:Tumor rejection by modulation of tumor stromal fibroblasts
Creators Name:Schueler, T. and Koernig, S. and Blankenstein, T.
Abstract:Interleukin (IL)-4-secreting tumors are rejected in mice, an effect that is thought to be immune mediated. However, solid tumors are embedded in a stroma that often contains tumor-promoting fibroblasts, a cell population whose function is also affected by IL-4. Here we show that IL-4-secreting tumors grew undiminished in IL-4 receptor (R)-deficient (IL-4R-/-) mice. In IL-4R+/+ mice they were long-term suppressed in the absence of T cells but complete rejection required T cells, compatible with the assumption that hematopoietic cells needed to respond to IL-4. Surprisingly, bone marrow (BM) chimeric mice revealed that IL-4R expression exclusively on non-BM-derived cells was sufficient for tumor rejection. Fibroblasts in the tumor stroma were identified as a target cell type for IL-4 because they accumulated in IL-4-secreting tumors and displayed an activated phenotype. Additionally, coinjection of IL-4R+/+ but not IL-4R-/- fibroblasts was sufficient for the rejection of IL-4-secreting tumors in IL-4R-/- mice. Our data demonstrate a novel mechanism by which IL-4 contributes to tumor rejection and show that the targeted modulation of tumor-associated fibroblasts can be sufficient for tumor rejection.
Keywords:IL-4 Receptor, Bone Marrow Transplantation, Angiogenesis, Collagen, Animals, Mice
Source:Journal of Experimental Medicine
ISSN:0022-1007
Publisher:Rockefeller University Press (U.S.A.)
Volume:198
Number:10
Page Range:1487-1493
Date:17 November 2003
Official Publication:https://doi.org/10.1084/jem.20030849
PubMed:View item in PubMed

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