SFB 685 "Immunotherapy: Molecular basis and clinical application" - Teilprojekt TP C01 "Induktion eines dauerhaften Wachstumsarrests in Tumoren mittels CD4 T Helfer-Zellen"

01/07/2013 to 30/06/2017

Gene mutations leading to accelerated cell cycle are frequent cancer driver mutations and normally targeted by small molecules. We found that, surprisingly, Th1 cell cytokines can induce senescence-like cell cycle arrest directly, even in T antigen (Tag) expressing cancers.
Tag-specific Th1 cells arrest cancers, through IFN-γ and TNFR1 driven activation of the p16INK4a/Rb senescence pathway, and obviously preserve genomic stability. As Rb is non-redundant for cell cycle control we will now study a) the exact signaling pathways by which TNFR1-signaling activates p16INK4a/Rb in concert with IFN-γ and b) the genetic effects of Rb-mediated E2F2 suppression and gene silencing.