Interfaces between cellular responses to DNA damage and cancer immunotherapy

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• The DNA damage response (DDR) is crucial for maintaining genome stability.
• Targeting DDR pathways, such as with PARP inhibitors, has shown success in cancer therapy.
• Emerging evidence links DDR to innate and adaptive immune responses in tumors.

Purpose of the Study:

• To review the molecular mechanisms of DNA damage-triggered immune responses.
• To highlight the role of DDR components in the efficacy of immune checkpoint inhibitors (ICIs).
• To discuss the potential of combining DDR inhibitors with ICIs.

Main Methods:

• Literature review of studies on DDR, cancer immunity, and immunotherapy.
• Analysis of molecular pathways linking DNA damage sensing (e.g., cGAS/STING) to immune signaling.
• Evaluation of clinical implications and therapeutic strategies.

Main Results:

• DDR factors can modulate chronic inflammatory signaling and influence antitumor immunity.
• DDR components may serve as biomarkers for ICI therapy response.
• DDR inhibitors can impact the tumor microenvironment and immune cell function.

Conclusions:

• Understanding DDR-immune interactions is key for optimizing cancer therapy.
• Combining DDR inhibitors with ICIs presents a promising therapeutic avenue.
• Further research is needed to overcome hindrances for broader clinical application of these combinations.