Radiation as an immune modulator: mechanisms and implications for combination with immunotherapy

Area of Science:

• Oncology
• Immunology
• Radiation Oncology

Background:

• Radiation therapy kills cancer cells and modulates the immune system.
• Immune checkpoint blockade (ICB) combined with radiation therapy can improve tumor control in some cancers.
• However, most combination trials lack clinical benefit, and predictive biomarkers are needed.

Purpose of the Study:

• To review how radiation parameters influence immunological responses in combination with ICB.
• To reconcile mechanistic insights with clinical trial outcomes.
• To provide rationale for developing immunologically informed radiation protocols.

Main Methods:

• Review of current literature on radiation therapy, ICB, and their combination.
• Analysis of how radiation dose, fractionation, and treatment volume affect local and systemic immunity.
• Examination of mechanistic insights and clinical trial data.

Main Results:

• Radiation dose, fractionation, and volume significantly impact the balance between immunostimulation and immunosuppression.
• Protocols optimized for direct tumor kill may not be optimal for immune synergy with ICB.
• Heterogeneous clinical outcomes reflect gaps in understanding radiation's immunological effects.

Conclusions:

• Developing immunologically informed radiation protocols is crucial for maximizing the potential of radioimmunotherapy combinations.
• Transitioning from empirical to tailored combinations may improve patient survival.
• Further research is needed to optimize radiation parameters for enhanced immunotherapy efficacy.