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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 |
| 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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