The abscopal effect: a sense of DNA damage is in the air

J Clin Invest. 2021 May 3;131(9):e148274. doi: 10.1172/JCI148274.


Tumor metastasis is a singularly important determinant of survival in most cancers. Historically, radiation therapy (RT) directed at a primary tumor mass was associated infrequently with remission of metastasis outside the field of irradiation. This away-from-target or "abscopal effect" received fringe attention because of its rarity. With the advent of immunotherapy, there are now increasing reports of abscopal effects upon RT in combination with immune checkpoint inhibition. This sparked investigation into underlying mechanisms and clinical trials aimed at enhancement of this effect. While these studies clearly attribute the abscopal effect to an antitumor immune response, the initial molecular triggers for its onset and specificity remain enigmatic. Here, we propose that DNA damage-induced inflammation coupled with neoantigen generation is essential during this intriguing phenomenon of systemic tumor regression and discuss the implications of this model for treatment aimed at triggering the abscopal effect in metastatic cancer.

Publication types

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

MeSH terms

  • Animals
  • Combined Modality Therapy
  • DNA Damage / immunology*
  • DNA, Neoplasm / immunology*
  • Humans
  • Immunotherapy*
  • Neoplasm Metastasis
  • Neoplasms* / immunology
  • Neoplasms* / pathology
  • Neoplasms* / therapy


  • DNA, Neoplasm