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Updated: Aug 3, 2025
Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells
Published on: June 9, 2020
The DNA Damage Response and Inflammation in Cancer
Vanessa Klapp1,2,3, Beatriz Álvarez-Abril1,4, Giuseppe Leuzzi5,6,7
1Department of Radiation Oncology, Weill Cornell Medical College, New York, New York.
Abstract:
Genomic stability in normal cells is crucial to avoid oncogenesis. Accordingly, multiple components of the DNA damage response (DDR) operate as bona fide tumor suppressor proteins by preserving genomic stability, eliciting the demise of cells with unrepairable DNA lesions, and engaging cell-extrinsic oncosuppression via immunosurveillance. That said, DDR sig-naling can also favor tumor progression and resistance to therapy. Indeed, DDR signaling in cancer cells has been consistently linked to the inhibition of tumor-targeting immune responses. Here, we discuss the complex interactions between the DDR and inflammation in the context of oncogenesis, tumor progression, and response to therapy.
Significance:
Accumulating preclinical and clinical evidence indicates that DDR is intimately connected to the emission of immunomodulatory signals by normal and malignant cells, as part of a cell-extrinsic program to preserve organismal homeostasis. DDR-driven inflammation, however, can have diametrically opposed effects on tumor-targeting immunity. Understanding the links between the DDR and inflammation in normal and malignant cells may unlock novel immunotherapeutic paradigms to treat cancer.
Insights
The DNA damage response (DDR) maintains genomic stability but can also promote cancer by inhibiting anti-tumor immunity. Understanding DDR
Area of Science:
- Molecular Biology
- Immunology
- Oncology
Background:
- Genomic stability is essential for preventing cancer, with DNA damage response (DDR) pathways acting as tumor suppressors.
- DDR mechanisms include promoting cell death and immune surveillance.
- However, DDR signaling can paradoxically support tumor progression and treatment resistance.
Purpose of the Study:
- To explore the intricate relationship between the DNA damage response (DDR) and inflammation in cancer.
- To discuss how DDR influences oncogenesis, tumor progression, and therapeutic responses.
- To highlight the dual role of DDR-driven inflammation in modulating anti-tumor immunity.
Main Methods:
- Review of preclinical and clinical evidence.
- Analysis of molecular mechanisms linking DDR and immune signaling.
- Discussion of therapeutic implications.
Main Results:
- DDR is intrinsically linked to the release of immunomodulatory signals from both normal and cancer cells.
- DDR-induced inflammation can either enhance or suppress anti-tumor immune responses.
- DDR signaling in cancer cells often correlates with the inhibition of immune responses targeting tumors.
Conclusions:
- The interplay between DDR and inflammation is complex, impacting cancer development and treatment.
- Understanding these interactions may reveal new avenues for cancer immunotherapy.
- Targeting DDR-mediated inflammation could offer novel therapeutic strategies.
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