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 bis 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.