Soluble type II transforming growth factor-beta receptor inhibits established murine malignant mesothelioma tumor growth by augmenting host antitumor immunity
| Autor: | Veena Kapoor, Peter DeLong, Eiji Suzuki, H.-Kam Cheung, Steven M. Albelda, Leona E. Ling, Larry R. Kaiser |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
CD4-Positive T-Lymphocytes
Mesothelioma Cancer Research medicine.medical_specialty Ratón Genes MHC Class II Genes MHC Class I Mice SCID Biology CD8-Positive T-Lymphocytes Protein Serine-Threonine Kinases Lymphocyte Depletion Transforming Growth Factor beta1 Mice Transforming Growth Factor beta3 Peritoneum Transforming Growth Factor beta Internal medicine medicine Tumor Cells Cultured Animals fas Receptor Receptor Mice Inbred BALB C Receptor Transforming Growth Factor-beta Type II medicine.disease Blockade Cytolysis medicine.anatomical_structure Endocrinology Oncology Cancer research Mice Inbred CBA Female Receptors Transforming Growth Factor beta CD8 Spleen Transforming growth factor T-Lymphocytes Cytotoxic |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 10(17) |
| ISSN: | 1078-0432 |
| Popis: | Purpose: Transforming growth factor (TGF)-β blockade has been proposed as an anticancer therapy; however, understanding which tumor patients might benefit most from such therapy is crucial. An ideal target of such inhibitory therapy might be malignant mesothelioma (MM), a highly lethal, treatment-resistant malignancy of mesothelial cells of the pleura and peritoneum that produces large amounts of TGF-β. The purpose of this study was to explore the possible therapeutic utility of TGF-β blockade on MM. Experimental Design: To evaluate this hypothesis, we tested the effects of a soluble TGF-β type II receptor (sTGF-βR) that specifically inhibits TGF-β1 and TGF-β3 in three different murine MM tumor models, AB12 and AC29 (which produce large amounts of TGF-β) and AB1 (which does not produce TGF-β). Results: Tumor growth of both established AB12 and AC29 tumors was inhibited by sTGF-βR. In contrast, AB1 tumors showed little response to sTGF-βR. The mechanism of these antitumor effects was evaluated and determined to be primarily dependent on immune-mediated responses because (a) the antitumor effects were markedly diminished in severe combined immunodeficient mice or mice depleted of CD8+ T cells and (b) CD8+ T cells isolated from spleens of mice treated with sTGF-βR showed strong antitumor cytolytic effects, whereas CD8+ T cells isolated from spleens of tumor-bearing mice treated with of control IgG2a showed no antitumor cytolytic effects. Conclusions: Our data suggest that TGF-β blockade of established TGF-β-secreting MM should be explored as a promising strategy to treat patients with MM and other tumors that produce TGF-β. |
| Databáze: | OpenAIRE |
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