Radiation-induced equilibrium is a balance between tumor cell proliferation and T cell–mediated killing

H Liang, L Deng, S Chmura, B Burnette… - The Journal of …, 2013 - journals.aai.org
H Liang, L Deng, S Chmura, B Burnette, N Liadis, T Darga, MA Beckett, MW Lingen, ME Witt…
The Journal of Immunology, 2013journals.aai.org
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 …
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.
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