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The DNA damage response in immunotherapy and radiation

Robert M Samstein1, Nadeem Riaz1

  • 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Advances in Radiation Oncology
|October 30, 2018
PubMed
Abstract

Insights

Exploiting DNA damage repair (DDR) defects in tumors with therapies like radiation can enhance anti-tumor immunity. Combining DDR targeting agents with immune checkpoint inhibitors (ICI) shows promise for advanced cancer treatment.

Area of Science:

  • Oncology
  • Cancer Immunology
  • Molecular Biology

Background:

  • Deficiencies in DNA damage repair (DDR) are common in tumors.
  • Targeting DDR defects therapeutically is an emerging strategy.
  • DDR defects influence tumor immunogenicity and response to immunotherapy.

Purpose of the Study:

  • To review the interplay between DDR pathways, radiation, and immune checkpoint inhibitor (ICI) efficacy.
  • To describe mechanisms of radiation-induced immunogenicity.
  • To highlight the potential of combination therapies.

Main Methods:

  • Literature review of studies on DDR, radiation, and immunotherapy.
  • Analysis of mechanisms linking DDR defects to immune responses.
  • Discussion of clinical implications for combination therapeutics.

Main Results:

  • DDR defects and ionizing radiation can enhance tumor immunogenicity.
  • Cytosolic DNA sensing pathways, such as cGAS/STING, mediate radiation-induced immune responses.
  • Somatic mutations and DDR defects predict response to ICI.

Conclusions:

  • Understanding the DDR-immune system interaction is crucial for advancing cancer immunotherapy.
  • Combination of DDR targeting agents with ICI offers a promising therapeutic avenue for advanced cancers.
  • Further research into these mechanisms will expand immunotherapy's potential.

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