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Published on: October 20, 2016
Consensus statement on microglial and macrophage functions in gliomas
Yuqi Zheng1, Islam Alzoubi2, Manuel B Graeber3
1Ken Parker Brain Tumour Research Laboratories, Brain and Mind Centre, University of Sydney, Camperdown, Australia.
Abstract:
This international consensus statement synthesizes key findings on the complex roles of microglia and macrophages (tumor-associated microglia/macrophages or TAMs) in glioma progression and therapeutic resistance. Recent advances have highlighted the cellular, spatial, and temporal heterogeneity of TAMs, their functional plasticity, and the intricate interactions between TAMs, glioma stem cells, and the neuronal microenvironment, challenging the M1/M2 classification paradigm for TAMs in gliomas and other misconceptions. The statement emphasizes that glioma cells manipulate TAMs to suppress anti-tumor functions, while microglia-mediated modulation of neuron-glioma cell interactions promotes tumor progression. Furthermore, glioblastoma-derived extracellular vesicles (EVs) reprogram microglia to support tumor progression, offering novel therapeutic targets. To advance research and develop more effective treatments, the statement advocates for precision therapies targeting specific TAM subsets or functions, the use of bioengineered EVs as a therapeutic approach, and a shift away from simplistic terminology like "M1/M2" and "neuroinflammation". Ultimately, this new understanding can support innovative strategies to modulate the tumor microenvironment, turning immunosuppression into immunostimulation and improving outcomes for patients with glioblastoma and other types of gliomas.
Insights
Glioma cells manipulate microglia and macrophages (tumor-associated microglia/macrophages or TAMs) to promote tumor growth and resistance. Targeting specific TAMs or using engineered extracellular vesicles offers new therapeutic strategies for glioma.
Area of Science:
- Neuro-oncology
- Immunology
- Cell Biology
Background:
- Microglia and macrophages, collectively known as tumor-associated microglia/macrophages (TAMs), play complex roles in glioma progression and therapeutic resistance.
- Recent research reveals significant heterogeneity, plasticity, and intricate interactions of TAMs within the glioma microenvironment, challenging traditional classifications.
Purpose of the Study:
- To synthesize current knowledge on TAMs in glioma, moving beyond simplistic M1/M2 paradigms.
- To highlight novel therapeutic targets and strategies for glioma treatment based on TAM function and interaction with the tumor microenvironment.
Main Methods:
- International consensus statement synthesizing recent findings from preclinical and clinical glioma research.
- Analysis of cellular, spatial, and temporal heterogeneity of TAMs and their interactions with glioma cells, stem cells, and neurons.
Main Results:
- Glioma cells actively manipulate TAMs to suppress anti-tumor immunity and promote progression.
- Microglia influence neuron-glioma interactions, fostering tumor advancement.
- Extracellular vesicles derived from glioblastoma can reprogram microglia to support tumor growth, representing potential therapeutic targets.
Conclusions:
- A paradigm shift is needed away from simplistic M1/M2 classifications and 'neuroinflammation' terminology.
- Precision therapies targeting specific TAM subsets or functions, alongside bioengineered extracellular vesicles, show promise for treating gliomas.
- Modulating the tumor microenvironment to convert immunosuppression into immunostimulation is key to improving patient outcomes in glioblastoma and other gliomas.
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