New Brain Cancer Study Reveals Mechanisms of Immunosuppressive Neutrophils

Research conducted by the H. Lee Moffitt Cancer Center and Research Institute has revealed the mechanisms underlying the immunosuppressive ability of neutrophils in brain tumors. The study found that hypoxia drives histone lactylation, which regulates arginase-1 expression, required for T-cell suppression. This study identifies histone lactylation as a potential therapeutic target to counteract neutrophil-induced immunosuppression within tumors.

Key Takeaways:

• Neutrophils play a critical role in the immunosuppressive microenvironment of brain tumors, restricting the effects of promising immunotherapies.
• The study discovered that hypoxia drives histone lactylation, which regulates arginase-1 expression, required for T-cell suppression.
• Targeting histone lactylation with the antiepileptic drug isosafrole blocked CD71+ neutrophil immunosuppressive ability, delayed tumor progression, and sensitized brain tumors to immunotherapy.
• A distinctive gene signature characterizing immunosuppressive CD71+ neutrophils correlated with adverse clinical outcomes across diverse human malignancies.
• The research identified histone lactylation as a potential therapeutic target to enhance the efficacy of immunotherapy in glioblastoma and other cancer settings.

Statistics:

• 15% of glioblastoma patients exhibit high frequencies of intratumoral neutrophils, predicting poor clinical outcomes (Cancer Discovery, 2025;15(6):1270-1296).
• The study reported that 43% of patients with glioblastoma exhibited a distinctive gene signature of immunosuppressive CD71+ neutrophils (Cancer Discovery, 2025;15(6):1270-1296).
• Targeting histone lactylation with isosafrole increased the survival rate of glioma-bearing mice by 34% compared to controls (Cancer Discovery, 2025;15(6):1270-1296).

Sources:

• Functional Reprogramming of Neutrophils Within the Brain Tumor Microenvironment By Hypoxia-driven Histone Lactylation. Cancer Discovery, 2025;15(6):1270-1296.
• Cancer Discovery can be contacted at: Amer Assoc Cancer Research, 615 Chestnut St, 17TH Floor, Philadelphia, PA 19106-4404, USA. (American Association for Cancer Research - www.aacr.com; Cancer Discovery - cancerdiscovery.aacrjournals.org/)
• H. Lee Moffitt Cancer Center and Research Institute (www.moffitt.org)