title: Changing T-cell enigma: cancer killing or cancer control?
abstract: Data from different laboratories and theoretical considerations challenge our current view on anticancer immunity. Immune cells are capable of destroying cancer cells under in vitro and in vivo conditions. Therefore, cellular immunity is considered to control cancers through mechanisms that kill cancers. Yet, therapeutic anticancer immune responses rarely delete cancers. If efficient, they rather establish a life with stable disease. This raises the question of whether killing is the sole mechanism by which immune therapy attacks cancers. Here, we show that, besides cancer eradication by cytotoxic lymphocytes, other modes of action are operative and strictly required for cancer control. We show that T helper-1 cells arrest cancer growth by driving cancers into a state of stable or permanent growth arrest, called senescence. Such immune cells establish cytokine-producing walls around developing cancers. When producing interferon-γ and tumor necrosis factor, this cytokine-induced tumor immune-surveillance keeps the cancer cells in a permanently non-proliferating state. Simultaneously, antiangiogenic chemokines cut their connections to the surrounding tissues. This strategy significantly reduces tumor burden and prolongs life of cancer-bearing animals. As human cancers also undergo senescence, the current data suggest tumor-immune surveillance through cytokine-induced senescence, instead of tumor eradication, as the more realistic and primary goal of cancer control.
authors.affiliation: Department of Dermatology; Eberhard Karls University; Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wieder
authors.forename: Heidi
authors.initials: H
authors.lastname: Braumüller
authors.forename: Ellen
authors.initials: E
authors.lastname: Brenner
authors.forename: Lars
authors.initials: L
authors.lastname: Zender
authors.forename: Martin
authors.initials: M
authors.lastname: Röcken
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D059447:Cell Cycle Checkpoints; D016922:Cellular Senescence; D018925:Chemokines / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D018925:Chemokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: T helper-1 cells; cancer therapy; cell cycle control; growth arrest; immune therapy; interferon-γ; p16Ink4a; senescence; tumor dormancy; tumor necrosis factor