Author/Authors :
Müller-Hermelink، نويسنده , , Nele and Braumüller، نويسنده , , Heidi and Pichler، نويسنده , , Bernd and Wieder، نويسنده , , Thomas and Mailhammer، نويسنده , , Reinhard and Schaak، نويسنده , , Katrin and Ghoreschi، نويسنده , , Kamran and Yazdi، نويسنده , , Amir and Haubner، نويسنده , , Roland and Sander، نويسنده , , Christian A. and Mocikat، نويسنده , , Ralph and Schwaiger، نويسنده , , Markus and Fِrster، نويسنده , , Irmgard and Huss، نويسنده , , Ralph and Weber، نويسنده , , Wolfgang A. and Kneilling، نويسنده , , Manfred and Rِcken، نويسنده , , Martin، نويسنده ,
Abstract :
Summary
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.
