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

J Immunol. 2013 Jun 1;190(11):5874-81. doi: 10.4049/jimmunol.1202612. Epub 2013 Apr 29.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cytotoxicity, Immunologic*
  • Disease Models, Animal
  • Humans
  • Immunotherapy
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Mice
  • Neoplasm Metastasis
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / surgery
  • Programmed Cell Death 1 Receptor
  • Radiosurgery
  • T-Lymphocytes / immunology*
  • Tumor Burden / immunology
  • Tumor Burden / radiation effects

Substances

  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor
  • Interferon-gamma