Radiotherapy, immunity, and immune checkpoint inhibitors

Area of Science:

• Oncology
• Immunology
• Radiation Oncology

Background:

• Radiotherapy (RT) has dual effects on the immune system, both locally in the tumor microenvironment and systemically.
• Preclinical studies suggested synergy between RT and immune checkpoint inhibitors (ICIs), leading to clinical trials.

Purpose of the Study:

• To review the immunostimulatory effects of RT that underpinned combination trials with ICIs.
• To analyze clinical trial outcomes of radioimmunotherapy in light of RT's immunosuppressive effects.
• To identify strategies to mitigate RT-induced immunosuppression for improved therapeutic efficacy.

Main Methods:

• Literature review of preclinical data on RT-induced immune responses.
• Analysis of published clinical trial results for radioimmunotherapy.
• Examination of the mechanisms underlying RT-induced immunosuppression.

Main Results:

• Early optimism for radioimmunotherapy was not consistently met in clinical trials.
• Both curative and metastatic settings have shown limited success for combined RT-ICI treatments.
• RT's immunosuppressive effects may counteract its immunostimulatory potential in combination therapies.

Conclusions:

• Overcoming radiotherapy-induced immunosuppression is crucial for enhancing the efficacy of combined RT-ICI treatments.
• Targeting immunosuppressive pathways could unlock the full potential of radioimmunotherapy.
• Further research is needed to optimize combination strategies for better patient outcomes.