Prolonged interval hypofractionated radiotherapy facilitates better antitumor immunity

Area of Science:

• Radiation Oncology
• Cancer Immunology
• Immunotherapy

Background:

• Hypofractionated radiotherapy (Hypo-RT) involves delivering higher doses of radiation per fraction.
• Optimizing Hypo-RT schedules is crucial for maximizing therapeutic efficacy while minimizing toxicity.
• Understanding the interplay between radiation fractionation, tumor response, and immune activation is essential for novel cancer treatment strategies.

Purpose of the Study:

• To investigate the impact of varying interfraction intervals in Hypo-RT on tumor growth.
• To assess the effects of different Hypo-RT regimens on the host immune response.
• To evaluate the synergistic potential of Hypo-RT with anti-PD-1 immunotherapy.

Main Methods:

• Utilized the mouse MC38 colon cancer model.
• Designed diverse radiation regimens varying fraction interval and size.
• Assessed tumor growth inhibition, immune cell mobilization, and combination effects with anti-PD-1 immunotherapy.

Main Results:

• Longer interfraction intervals in Hypo-RT (e.g., every other day, twice weekly) enhanced immune response compared to once-daily fractionation.
• Fixed biologically equivalent dose experiments showed similar tumor suppression between long-interval Hypo-RT and conventional daily fractionation.
• All Hypo-RT regimens combined with anti-PD-1 immunotherapy demonstrated superior tumor growth delay and increased intratumoral CD8+ T cells compared to conventional fractionation.

Conclusions:

• Prolonged interfraction intervals and increased fraction sizes in Hypo-RT can effectively balance tumor control and immune activation.
• Hypo-RT with extended interfraction intervals may offer a promising strategy for enhancing the efficacy of immunotherapy.