Fichtner-Feigl, Stefan and Terabe, Masaki and Kitani, Atsushi and Young, Cheryl A. and Fuss, Ivan and Geissler, Edward K. and Schlitt, Hans-Juergen and Berzofsky, Jay A. and Strober, Warren (2008) Restoration of tumor immunosurveillance via targeting of interleukin-13 receptor-alpha(2). CANCER RESEARCH, 68 (9). pp. 3467-3475. ISSN 0008-5472,
Full text not available from this repository. (Request a copy)Abstract
In previous studies, we described a "counter-immunosurveiHance" mechanism initiated by tumor-activated, interleukin-13 (IL-13)-producing natural killer T cells that signal Gr-1(+) cells to produce transforming growth factor-beta(1) (TGF-beta(1)), a cytokine that suppresses the activity of tumor-inhibiting cytolytic CD8(+) T cells. Here, we show that in two tumor models (the CT-26 metastatic colon cancer and the 15-12RM fibrosarcoma regressor models), this counter-surveillance mechanism requires the expression of a novel IL-13 receptor, IL-13R alpha(2), on Gr-1(intermediate) cells, because down-regulation of IL-13R alpha(2) expression or the activator protein-1 signal generated by the receptor via in vivo administration of specific small interfering RNA or decoy oligonucleotides leads to loss of TGF-beta(1) production. Furthermore, acting on prior studies showing that IL-13R alpha(2) expression is induced (in part) by tumor necrosis factor-alpha (TNF-alpha),we show that receptor expression and TGF-alpha production is inhibited by administration of a TNF-alpha-neutralizing substance, TNF-alpha R-Fc(etanereept). Taking advantage of this latter fact, we then show in the CT-26 model that counter-immunosurveillance can he inhibited, anti-CT-26-specific CD8(+) cytolytic activity can be restored, and CT-26 metastatic tumor nodules can be greatly decreased by administration of TNF-alpha R-Fc. Corroborative data were obtained using the 15-12RM fibrosarcoma model. These studies point to the prevention of metastatic cancer with an available agent with already known clinically acceptable adverse effects and toxicity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NECROSIS-FACTOR-ALPHA; T-CELLS; ANTITUMOR IMMUNITY; IL-13 RECEPTOR; FIBROSIS; GROWTH; CANCER; CYTOTOXICITY; INDUCTION; ARTHRITIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Nov 2020 07:50 |
| Last Modified: | 03 Nov 2020 07:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30926 |
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