The abscopal effect of radiation therapy

Future Oncol. 2021 May;17(13):1683-1694. doi: 10.2217/fon-2020-0994. Epub 2021 Mar 17.

Abstract

Radiation therapy (RT) in some cases results in a systemic anticancer response known as the abscopal effect. Multiple hypotheses support the role of immune activation initiated by RT-induced DNA damage. Optimal radiation dose is necessary to promote the cGAS-STING pathway in response to radiation and initiate an IFN-1 signaling cascade that promotes the maturation and migration of dendritic cells to facilitate antigen presentation and stimulation of cytotoxic T cells. T cells then exert a targeted response throughout the body at areas not subjected to RT. These effects are further augmented through the use of immunotherapeutic drugs resulting in increased T-cell activity. Tumor-infiltrating lymphocyte presence and TREX1, KPNA2 and p53 signal expression are being explored as prognostic biomarkers.

Keywords: abscopal effect; autologous tumor vaccine; immunotherapy; radiation therapy/radiotherapy; vaccines.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism
  • Cell Movement / radiation effects
  • Chemoradiotherapy / methods*
  • Clinical Trials as Topic
  • DNA Damage / immunology
  • DNA Damage / radiation effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / radiation effects
  • Exodeoxyribonucleases / analysis
  • Exodeoxyribonucleases / metabolism
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / radiation effects
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / mortality
  • Neoplasms / radiotherapy*
  • Phosphoproteins / analysis
  • Phosphoproteins / metabolism
  • Prognosis
  • Progression-Free Survival
  • Radiotherapy Dosage
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / radiation effects
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology
  • Tumor Microenvironment / radiation effects
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / metabolism
  • alpha Karyopherins / analysis
  • alpha Karyopherins / metabolism

Substances

  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • KPNA2 protein, human
  • Phosphoproteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • alpha Karyopherins
  • Exodeoxyribonucleases
  • three prime repair exonuclease 1