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

Hua Liang, Liufu Deng, Steven Chmura, Byron Burnette, Nicole Liadis, Thomas Darga, Michael A. Beckett, Mark W. Lingen, Mary Ellyn Witt, Ralph R. Weichselbaum, Yang Xin Fu

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)5874-5881
Number of pages8
JournalJournal of Immunology
Volume190
Issue number11
DOIs
StatePublished - Jun 1 2013

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Cell Proliferation
Radiation
T-Lymphocytes
Neoplasms
Animal Models
Intrinsic Factor
Angiogenesis Inducing Agents
Cell Death
Radiotherapy
Parturition
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Radiation-induced equilibrium is a balance between tumor cell proliferation and T cell-mediated killing. / Liang, Hua; Deng, Liufu; Chmura, Steven; Burnette, Byron; Liadis, Nicole; Darga, Thomas; Beckett, Michael A.; Lingen, Mark W.; Witt, Mary Ellyn; Weichselbaum, Ralph R.; Fu, Yang Xin.

In: Journal of Immunology, Vol. 190, No. 11, 01.06.2013, p. 5874-5881.

Research output: Contribution to journalArticle

Liang, H, Deng, L, Chmura, S, Burnette, B, Liadis, N, Darga, T, Beckett, MA, Lingen, MW, Witt, ME, Weichselbaum, RR & Fu, YX 2013, 'Radiation-induced equilibrium is a balance between tumor cell proliferation and T cell-mediated killing', Journal of Immunology, vol. 190, no. 11, pp. 5874-5881. https://doi.org/10.4049/jimmunol.1202612
Liang, Hua ; Deng, Liufu ; Chmura, Steven ; Burnette, Byron ; Liadis, Nicole ; Darga, Thomas ; Beckett, Michael A. ; Lingen, Mark W. ; Witt, Mary Ellyn ; Weichselbaum, Ralph R. ; Fu, Yang Xin. / Radiation-induced equilibrium is a balance between tumor cell proliferation and T cell-mediated killing. In: Journal of Immunology. 2013 ; Vol. 190, No. 11. pp. 5874-5881.
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