The DNA damage induced immune response: Implications for cancer therapy

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Updated: Aug 23, 2025

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells
05:18

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells

Published on: June 9, 2020

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Eliana M Barros1, Stuart A McIntosh1, Kienan I Savage1

  • 1Patrick G Johnston Centre for Cancer Research & Cell Biology, Queen's University Belfast, 97 Lisburn Rd, Belfast BT9 7AE, UK.

DNA Repair
|October 29, 2022
PubMed

Insights

Defects in DNA damage response (DDR) pathways can activate the cGAS/STING innate immune pathway, influencing cancer development and treatment. This interplay offers new therapeutic strategies combining DNA damage agents with immunotherapies.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Genomic instability is a key feature of cancer, impacting tumor progression and treatment outcomes.
  • Deficiencies in DNA damage response (DDR) pathways are increasingly recognized for their role in shaping therapeutic responses, particularly with immune checkpoint blockade (ICB) therapy.
  • The cGAS/STING signaling pathway is a critical mediator of inflammation in response to DNA damage.

Approach:

  • Transcriptional profiling of BRCA1/2 deficient breast cancers and Fanconi Anaemia (FA) patient bone marrow identified a common subgroup with upregulated innate immune signaling.
  • The study reviews the literature on intrinsic and extrinsic DNA damage in mediating immune activation.
  • The review explores the context of DNA damage-induced immune responses within tumorigenesis.

Key Points:

  • DNA damage response defects, such as those in BRCA1/2 and FA, are linked to the activation of innate immune signaling via the cGAS/STING pathway.
  • DNA damage, whether from inherent repair defects or external agents like chemotherapy and radiation, can trigger an innate immune response.
  • This immune activation presents potential therapeutic opportunities in cancer treatment.

Conclusions:

  • The interplay between DNA damage response pathways and the immune system, particularly via cGAS/STING, is crucial in cancer.
  • Understanding this connection opens avenues for novel cancer therapies, including the combination of DNA damaging agents with immunotherapies.
Keywords:
DNA-damage cGAS STING innate immune

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