1. TNFR1 Signaling and IFN-γ Signaling Determine whether T Cells Induce Tumor Dormancy or Promote Multistage Carcinogenesis
- Author
-
Müller-Hermelink, Nele, Braumüller, Heidi, Pichler, Bernd, Wieder, Thomas, Mailhammer, Reinhard, Schaak, Katrin, Ghoreschi, Kamran, Yazdi, Amir, Haubner, Roland, Sander, Christian A., Mocikat, Ralph, Schwaiger, Markus, Förster, Irmgard, Huss, Ralph, Weber, Wolfgang A., Kneilling, Manfred, and Röcken, Martin
- Subjects
- *
IMMUNE response , *IMMUNOLOGY , *TUMORS , *T cells , *CARCINOGENESIS , *CANCER cells - Abstract
Summary: Immune responses may arrest tumor growth by inducing tumor dormancy. The mechanisms leading to either tumor dormancy or promotion of multistage carcinogenesis by adaptive immunity are poorly characterized. Analyzing T antigen (Tag)-induced multistage carcinogenesis in pancreatic islets, we show that Tag-specific CD4+ T cells home selectively into the tumor microenvironment around the islets, where they either arrest or promote transition of dysplastic islets into islet carcinomas. Through combined TNFR1 signaling and IFN-γ signaling, Tag-specific CD4+ T cells induce antiangiogenic chemokines and prevent αvβ3 integrin expression, tumor angiogenesis, tumor cell proliferation, and multistage carcinogenesis, without destroying Tag-expressing islet cells. In the absence of either TNFR1 signaling or IFN-γ signaling, the same T cells paradoxically promote angiogenesis and multistage carcinogenesis. Thus, tumor-specific T cells can directly survey multistage carcinogenesis through cytokine signaling. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF