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The DNA damage response arouses the immune system
Stephan Gasser1, David H Raulet
1Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200, USA.
Abstract:
Although there is considerable knowledge of how DNA damage triggers cell cycle arrest, DNA repair, and apoptosis, little was known about its potential role in immune responses. Recently, we showed that genotoxic stress and stalled DNA replication forks induce the expression of ligands for the NKG2D receptor found in natural killer cells and certain T cells, cell types that are able to attack tumor cells. Chronic activation of this response in tumor cells may contribute to immune recognition, but it also imposes a selection mechanism for immune escape and malignant progression. This unique arm of the DNA damage response may have implications for understanding therapeutic responses, many of which induce the DNA damage response, and for designing more effective regimens to treat cancer.
Insights
DNA damage response activates immune cells to target cancer cells. However, this can lead to tumor immune escape and progression, impacting cancer therapy effectiveness.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- The DNA damage response (DDR) is well-understood in terms of cell cycle arrest, DNA repair, and apoptosis.
- Its role in modulating immune responses remained largely unknown.
Purpose of the Study:
- To investigate the link between DNA damage and immune system activation.
- To explore the implications of this connection for cancer therapy.
Main Methods:
- The study focused on genotoxic stress and stalled DNA replication forks.
- Expression levels of ligands for the NKG2D receptor were analyzed.
Main Results:
- Genotoxic stress and stalled replication forks were found to induce NKG2D receptor ligands.
- These ligands are expressed on natural killer cells and T cells, which attack tumor cells.
Conclusions:
- The DNA damage response can trigger anti-tumor immune responses via NKG2D ligands.
- Chronic activation may promote tumor immune escape and malignant progression.
- Understanding this pathway is crucial for improving cancer therapeutic strategies.
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