Eberhard-Karls-University Tubingen, Germany
Title: Cytokine-induced senescence in cancer therapy
Martin Rocken is Professor and Chairman of a large dermatology department, with a strong focus on clinical, experimental and translational oncology. He is member of major societies namely the German Academy of Sciences. He is/was executive board member of major journals, funding and research organizations. His lab, supported by public funds, characterized major signals allowing the antigen-specifi c induction of either TH1 or TH2 cells in vivo, fi rst in mice and then in humans, and established immune-based therapies. Recently, they fi rst described that immunity can arrest cancer by inducing senescence, a permanent growth arrest, even in the absence of killing.
Growing cancers are characterized by infi ltrating cancer cells, neo-angiogenesis and a cellular infi ltrate with immunosuppressive properties. As it is strongly believed that cancer immune-control strictly relies on the killing of individual cancer cells, and multiple approaches enhance the activity of tumor-reactive killer cel ls. While generally accepted, this view confl icts with the observation that effi cient anti-cancer immunity rarely eradicates cancer. Th us, effi cient immunotherapy of metastatic melanoma causes cancer regression and stable growth arrest rather than cancer eradication. Recent data now show that adaptive immunity can arrest cancers through signals mediated by the TH1 cytokines interferon (IFN) and tumor necrosis factor. When signaling together, IFN and TNF can induce a permanent growth arrestin cancers that is named senescence. Simultaneous action of IFN and TNF activates the p16/Rb-senescence pathway in a large spectrum of cancers. Effi cient activation oft he p16/Rb-senescence pathway drives even advanced cancers into senescence. Importantly, the TH1 cytokines IFN and TNF also induce senescence in a large spectrum of human cancers. Such senescent cancers share many similarities with premalignant tumors, including their failure to grow in an immune-incompetent environment. As cytokine-induced senescence can also arrest established cancers, treatment of established cancers by TH1 cytokines is currently investigated.