Stimulating Innate Immunity to Enhance Radiation Therapy-Induced Tumor Control

Int J Radiat Oncol Biol Phys. 2017 Oct 1;99(2):362-373. doi: 10.1016/j.ijrobp.2017.04.014. Epub 2017 Apr 19.

Abstract

Novel ligands that target Toll-like receptors and other innate recognition pathways represent a potent strategy for modulating innate immunity to generate antitumor immunity. Although many of the current clinically successful immunotherapies target adaptive T-cell responses, both preclinical and clinical studies suggest that adjuvants have the potential to enhance the scope and efficacy of cancer immunotherapy. Radiation may be a particularly good partner to combine with innate immune therapies, because it is a highly efficient means to kill cancer cells but may fail to send the appropriate inflammatory signals needed to act as an efficient endogenous vaccine. This may explain why although radiation therapy is a highly used cancer treatment, true abscopal effects-regression of disease outside the field without additional systemic therapy-are extremely rare. This review focuses on efforts to combine innate immune stimuli as adjuvants with radiation, creating a distinct and complementary approach from T cell-targeted therapies to enhance antitumor immunity.

Publication types

  • Review

MeSH terms

  • Combined Modality Therapy / methods
  • DEAD Box Protein 58 / metabolism
  • Humans
  • Immunity, Innate*
  • Immunotherapy / methods*
  • Membrane Proteins / metabolism
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / radiotherapy*
  • Receptor, Interferon alpha-beta / metabolism
  • Receptors, Immunologic
  • T-Lymphocytes / immunology
  • Toll-Like Receptor 3 / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Toll-Like Receptor 7 / metabolism
  • Toll-Like Receptor 9 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Membrane Proteins
  • Receptors, Immunologic
  • STING1 protein, human
  • TLR3 protein, human
  • TLR4 protein, human
  • TLR7 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptor 4
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • Tumor Necrosis Factor-alpha
  • Receptor, Interferon alpha-beta
  • RIGI protein, human
  • DEAD Box Protein 58