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Updated: Dec 22, 2025
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
Error-prone DNA repair pathways as determinants of immunotherapy activity: an emerging scenario for cancer treatment
Daniele Caracciolo1, Caterina Riillo1, Mariamena Arbitrio2
1Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy.
Abstract:
Defects in DNA repair machinery play a critical role in the pathogenesis and progression of human cancer. When they occur, the tumor cells activate error-prone mechanisms which lead to genomic instability and high mutation rate. These defects represent, therefore, a cancer Achilles'heel which could be therapeutically exploited by the use of DNA damage response inhibitors. Moreover, experimental and clinical evidence indicates that DNA repair deregulation has a pivotal role also in promoting immune recognition and immune destruction of cancer cells. Indeed, immune checkpoint inhibitors have received regulatory approval in tumors characterized by high genomic instability, such as melanomas and lung cancer. Here, we discuss how deregulation of DNA repair, through activation of error-prone mechanisms, increases immune activation against cancer. Finally, we address the potential strategies to use DNA repair components as biomarkers and/or therapeutic targets to empower immune-oncology treatment of human cancer.
Insights
Defects in DNA repair pathways drive cancer progression and genomic instability. Targeting these DNA repair defects can enhance anti-cancer immunity and improve immunotherapy outcomes.
Area of Science:
- Oncology
- Cancer Biology
- Immunology
Background:
- DNA repair defects are crucial in cancer development and progression.
- Tumor cells with DNA repair deficiencies activate error-prone mechanisms, leading to genomic instability and high mutation rates.
- These defects represent a vulnerability that can be therapeutically exploited.
Purpose of the Study:
- To discuss how DNA repair deregulation influences cancer immune recognition and destruction.
- To explore the potential of targeting DNA repair pathways to enhance cancer immunotherapy.
- To review DNA repair components as biomarkers and therapeutic targets in immuno-oncology.
Main Methods:
- Review of experimental and clinical evidence on DNA repair and cancer immunity.
- Analysis of the role of error-prone DNA repair mechanisms in immune activation.
- Discussion of therapeutic strategies involving DNA repair inhibitors and biomarkers.
Main Results:
- Deregulation of DNA repair, particularly through error-prone mechanisms, enhances anti-cancer immune responses.
- Tumors with high genomic instability, often linked to DNA repair defects, respond well to immune checkpoint inhibitors.
- DNA repair pathways are implicated in promoting immune recognition and destruction of cancer cells.
Conclusions:
- Targeting DNA repair defects offers a promising strategy to potentiate cancer immunotherapy.
- DNA repair components can serve as valuable biomarkers for predicting immunotherapy response.
- Exploiting DNA repair vulnerabilities can empower immune-oncology treatments for various human cancers.
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