Antitumor Effect by Either FLASH or Conventional Dose Rate Irradiation Involves Equivalent Immune Responses

Area of Science:

• Oncology
• Radiation Oncology
• Immunology

Background:

• Ultrahigh dose rate radiation therapy, known as FLASH, has shown promise for enhancing the therapeutic index of cancer treatment.
• The role of the immune system in mediating the antitumor effects of FLASH radiation therapy remains incompletely understood and requires rigorous evaluation.

Purpose of the Study:

• To investigate the contribution of the immune response to the antitumor efficacy of FLASH radiation therapy.
• To compare the immunomodulatory effects of FLASH and conventional (CONV) dose rate radiation therapy.

Main Methods:

• Utilized various murine tumor models in immunocompetent and immunocompromised mice.
• Administered single-dose (20 Gy) or hypofractionated regimens (3x8 Gy or 2x6 Gy) using FLASH (≥2000 Gy/s) and CONV (0.1 Gy/s) dose rates.
• Monitored tumor growth and performed immune profiling, with and without anti-CTLA-4 treatment.

Main Results:

• FLASH and CONV radiation therapy demonstrated isoeffective tumor growth delay across immunocompetent and moderately immunodeficient hosts.
• Profoundly immunocompromised mice also showed significant tumor growth delay with FLASH, indicating a potential immune-independent antitumor mechanism.
• Both irradiation modalities resulted in similar immune profiles, with decreased lymphoid cells and increased myeloid cells, and did not elevate TGF-β1 levels.

Conclusions:

• Tumor responses to FLASH radiation therapy are largely dose rate independent and do not rely heavily on the immune response.
• FLASH radiation therapy is as effective as CONV in modulating the antitumor immune response.
• FLASH radiation therapy can be utilized as an effective immunomodulatory agent in cancer treatment.