Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior

Area of Science:

• Neuro-oncology
• Immunology
• Surgical Oncology

Background:

• Glioblastoma (GBM) surgical interventions like biopsies and resections offer prognostic benefits.
• However, these procedures may also trigger negative responses, potentially promoting tumor progression.

Purpose of the Study:

• To investigate the negative effects of GBM biopsies on tumor cell behavior.
• To identify mechanisms driving these adverse effects and propose preventative strategies.

Main Methods:

• Retrospective patient study and intravital imaging in mice.
• High-resolution intravital microscopy to observe tumor cell responses to biopsy-like injury.
• Analysis of chemokine (C-C motif) ligand 2 (CCL-2) and macrophage involvement.
• Assessment of dexamethasone's effect on inflammatory response and tumor growth.

Main Results:

• Biopsy-like injury in GBM stimulates non-resected tumor cell proliferation and migration.
• This is mediated by CCL-2-dependent macrophage recruitment.
• Blocking macrophage recruitment or administering dexamethasone suppressed inflammation and subsequent tumor growth in mice and patients.
• These interventions were effective in both single and multifocal GBM cases.

Conclusions:

• Surgical procedures in GBM can paradoxically enhance tumor growth via inflammatory pathways.
• Inhibiting CCL-2-dependent macrophage recruitment presents a potential strategy to mitigate these adverse effects.
• Targeting macrophage recruitment may enhance the clinical benefits of GBM surgical interventions.