Neutrophils in glioma microenvironment: from immune function to immunotherapy

Area of Science:

• Neuro-oncology
• Immunology
• Cell Biology

Background:

• Glioma is a malignant central nervous system (CNS) tumor with limited effective treatments.
• Neutrophils, key components of the tumor microenvironment (TME), are increasingly recognized for their role in glioma.
• Recent discoveries highlight cranial-meningeal and intracranial lymphatic vessels, suggesting novel origins for CNS neutrophils.

Purpose of the Study:

• To review the molecular mechanisms of neutrophil infiltration into the CNS in the context of glioma.
• To detail the origin, functions, classifications, and targeted therapies of neutrophils in glioma.
• To explore the dual roles of neutrophils in glioma progression and their potential as immunotherapy targets.

Main Methods:

• Review of existing literature on neutrophil biology and glioma.
• Analysis of molecular mechanisms of neutrophil migration across the blood-brain barrier (BBB).
• Examination of neutrophil interactions within the glioma TME and with other immune cells.

Main Results:

• Neutrophils in the brain may originate from skull and vertebral bone marrow, entering via cranial-meningeal and lymphatic pathways.
• Neutrophils exhibit dual functions in glioma, contributing to malignant progression, immune suppression, and potential anti-tumor effects.
• Neutrophil infiltration and phenotypic changes are influenced by chemokines and tumor cell interactions.

Conclusions:

• Targeting neutrophils presents a promising avenue for a new generation of glioma immunotherapies.
• Understanding neutrophil origins and functions is crucial for developing effective cancer treatments.
• Modulating neutrophil activity within the TME could enhance the efficacy of current glioma therapies.