Proton Radiotherapy Offers Immune-Sparing Benefits in Glioblastoma Treatment

Area of Science:

• Oncology
• Radiation Oncology
• Immunology

Background:

• Glioblastoma (GB) and x-ray radiotherapy are linked to lymphopenia, negatively impacting prognosis and anti-tumor immunity.
• Proton therapy offers an alternative to x-rays, potentially reducing radiotoxicity due to its precise targeting of tumor tissue.

Purpose of the Study:

• To investigate and compare the effects of brain irradiation using x-rays versus protons on lymphopenia.
• To evaluate the impact on various immune cell populations and inform potential therapeutic strategies for glioblastoma.

Main Methods:

• Utilized GL261-tumor-bearing and tumor-free mouse models for evaluating lymphoid and myeloid cell populations.
• Assessed brain irradiation volume, beam orientation, and lymphopenia onset timing using flow cytometry.
• Quantified immune cells in the brain, cervical lymph nodes (CLN), and spleen, alongside plasma cytokine analysis.

Main Results:

• X-ray exposure induced severe lymphopenia (≥50% depletion) in various immune cells within 12 hours in tumor-free mice, with incomplete recovery.
• Proton therapy resulted in a milder decrease (15%) in circulating lymphocytes, with no significant myeloid cell reduction.
• Both radiation types affected T and B cells, with protons impacting CLNs but not the spleen, and cytokine levels correlated with leukocyte changes.

Conclusions:

• Proton therapy demonstrates a less severe lymphopenic effect compared to x-ray radiation.
• The observed differences in lymphopenia may stem from biological responses rather than solely reduced lymphocyte exposure.
• Findings support the potential integration of proton therapy with immunotherapy for glioblastoma treatment.