title: Cytokine-induced senescence for cancer surveillance.
abstract: The immune response is a first-line systemic defense to curb tumorigenesis and metastasis. Much effort has been invested to design antitumor interventions that would boost the immune system in its fight to defeat or contain cancerous growth. Tumor vaccination protocols, transfer of tumor-associated-antigen-specific T cells, T cell activity-regulating antibodies, and recombinant cytokines are counted among a toolbox filled with immunotherapeutic options. Although the mechanistic underpinnings of tumor immune control remain to be deciphered, these are studied with the goal of cancer cell destruction. In contrast, tumor dormancy is considered as a dangerous equilibrium between cell proliferation and cell death. There is, however, emerging evidence that tumor immune control can be achieved in the absence of overt cancer cell death. Here, we propose cytokine-induced senescence (CIS) by transfer of T helper-1 cells (TH1) or by recombinant cytokines as a novel therapeutic intervention for cancer treatment. Immunity-induced senescence triggers a stable cell cycle arrest of cancer cells. It engages the immune system to construct defensive, isolating barriers around tumors, and prevents tumor growth through the delivery or induction of TH1-cytokines in the tumor microenvironment. Keeping cancer cells in a non-proliferating state is a strategy, which directly copes with the lost homeostasis of aggressive tumors. As most studies show that even after efficient cancer therapies minimal residual disease persists, we suggest that therapies should include immune-mediated senescence for cancer surveillance. CIS has the goal to control the residual tumor and to transform a deadly disease into a state of silent tumor persistence.
authors.affiliation: Department of Dermatology, Eberhard Karls University, Liebermeisterstr. 25, 72076, Tübingen, Germany. thomas.wieder@med.uni-tuebingen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wieder
authors.affiliation: Department of Dermatology, Eberhard Karls University, Liebermeisterstr. 25, 72076, Tübingen, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Brenner
authors.affiliation: Department of Dermatology, Eberhard Karls University, Liebermeisterstr. 25, 72076, Tübingen, Germany.
authors.forename: Heidi
authors.initials: H
authors.lastname: Braumüller
authors.affiliation: Nuclear Organization and Oncogenesis Unit, Department of Cell Biology and Infection, Institut Pasteur, 28, Rue du Dr. Roux, 75724, Paris, France.|Inserm, U993, Paris, France.
authors.forename: Oliver
authors.initials: O
authors.lastname: Bischof
authors.affiliation: Department of Dermatology, Eberhard Karls University, Liebermeisterstr. 25, 72076, Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Röcken
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000276:immunology; D016922:Cellular Senescence / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D015166:Monitoring, Immunologic; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D016207:Cytokines
keywords: Cytokine-induced senescence; Inflammation; Receptor-mediated growth arrest; Tumor dormancy