title: Radiation-induced equilibrium is a balance between tumor cell proliferation and T cell-mediated killing.
abstract: Local failures following radiation therapy are multifactorial, and the contributions of the tumor and the host are complex. Current models of tumor equilibrium suggest that a balance exists between cell birth and cell death due to insufficient angiogenesis, immune effects, or intrinsic cellular factors. We investigated whether host immune responses contribute to radiation-induced tumor equilibrium in animal models. We report an essential role for immune cells and their cytokines in suppressing tumor cell regrowth in two experimental animal model systems. Depletion of T cells or neutralization of IFN-γ reversed radiation-induced equilibrium, leading to tumor regrowth. We also demonstrate that PD-L1 blockade augments T cell responses, leading to rejection of tumors in radiation-induced equilibrium. We identify an active interplay between tumor cells and immune cells that occurs in radiation-induced tumor equilibrium and suggest a potential role for disruption of the PD-L1/PD-1 axis in increasing local tumor control.
authors: Department of Radiation and Cellular Oncology, The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL 60637, USA.
authors: Hua
authors: H
authors: Liang
authors: Liufu
authors: L
authors: Deng
authors: Steven
authors: S
authors: Chmura
authors: Byron
authors: B
authors: Burnette
authors: Nicole
authors: N
authors: Liadis
authors: Thomas
authors: T
authors: Darga
authors: Michael A
authors: MA
authors: Beckett
authors: Mark W
authors: MW
authors: Lingen
authors: Maryellyn
authors: M
authors: Witt
authors: Ralph R
authors: RR
authors: Weichselbaum
authors: Yang-Xin
authors: YX
authors: Fu
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D061026:Programmed Cell Death 1 Receptor; D016634:Radiosurgery; D013601:T-Lymphocytes / Q000276:immunology*; D047368:Tumor Burden / Q000276:immunology / Q000528:radiation effects
chemical_list: D060890:B7-H1 Antigen; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma
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