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The DNA damage response and cancer immunotherapy

Sheng Hong1,2, Guo-Min Li3,4,5

  • 1Chinese Institute for Cancer Research, Chinese institutes for Medical Research, Beijing, China.

Nature Reviews. Cancer
|July 28, 2026
PubMed

Insights

DNA damage response (DDR) defects in cancer immunotherapy enhance immune response by generating immunogenic signals. This review explores how targeting DDR deficiencies can improve cancer treatment outcomes.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • The DNA damage response (DDR) and immune system are crucial for genomic integrity and host defense.
  • Their interplay is increasingly recognized as vital for cancer immunotherapy efficacy.

Purpose of the Study:

  • To review the molecular mechanisms linking DDR defects to enhanced immunotherapy response.
  • To discuss advances in DDR-targeted combination strategies and resistance mechanisms.

Main Methods:

  • Literature review of emerging research on DDR and cancer immunotherapy.
  • Analysis of molecular pathways involving genomic instability, neoantigens, and the cGAS-STING pathway.
  • Examination of clinical implications and therapeutic strategies.

Main Results:

  • DDR-deficient tumors or those treated with DDR inhibitors exhibit genomic instability, producing neoantigens and cytosolic DNA.
  • This stimulates the cGAS-STING pathway, increasing type I interferon and immune cell recruitment.
  • These effects synergize to improve responsiveness to immune checkpoint blockade.

Conclusions:

  • Exploiting DDR deficiencies offers a promising strategy to potentiate cancer immunotherapy.
  • DDR-targeted combination therapies and overcoming resistance are key to improving treatment outcomes.

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