Advances in Hypofractionated Irradiation-Induced Immunosuppression of Tumor Microenvironment

Front Immunol. 2021 Jan 25:11:612072. doi: 10.3389/fimmu.2020.612072. eCollection 2020.

Abstract

Hypofractionated radiotherapy is external beam irradiation delivered at higher doses in fewer fractions than conventional standard radiotherapy, which can stimulate innate and adaptive immunity to enhance the body's immune response against cancer. The enhancement effect of hypofractionated irradiation to immune response has been widely investigated, which is considered an approach to expand the benefit of immunotherapy. Meanwhile, increasing evidence suggests that hypofractionated irradiation may induce or enhance the suppression of immune microenvironments. However, the suppressive effects of hypofractionated irradiation on immunomicroenvironment and the molecular mechanisms involved in these conditions are largely unknown. In this context, we summarized the immune mechanisms associated with hypofractionated irradiation, highlighted the advances in its immunosuppressive effect, and further discussed the potential mechanism behind this effect. In our opinion, besides its immunogenic activity, hypofractionated irradiation also triggers homeostatic immunosuppressive mechanisms that may counterbalance antitumor effects. And this may suggest that a combination with immunotherapy could possibly improve the curative potential of hypofractionated radiotherapy.

Keywords: hypofractionated irradiation; immune microenvironment; immunosuppression; radiotherapy; tumor.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immune Tolerance / radiation effects*
  • Immunocompromised Host*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / radiotherapy*
  • Radiation Dose Hypofractionation*
  • Radiotherapy / adverse effects
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome
  • Tumor Escape / radiation effects
  • Tumor Microenvironment*