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Updated: Nov 29, 2025
In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
Long-lived tumor-associated macrophages in glioma
Petya B Georgieva1,2,3, Thomas Mathivet2,3, Silvanus Alt1
1Department: Cardiovascular and metabolic diseases, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Background:
The tumor microenvironment plays a major tumor-supportive role in glioma. In particular, tumor-associated macrophages (TAMs), which can make up to one-third of the tumor mass, actively support tumor growth, invasion, and angiogenesis. Predominantly alternatively activated (M2-polarized) TAMs are found in late-stage glioma in both human and mouse tumors, as well as in relapse samples from patients. However, whether tumor-educated M2 TAMs can actively contribute to the emergence and growth of relapse is currently debated.
Methods:
To investigate whether tumor-educated stromal cells remaining in the brain after surgical removal of the primary tumor can be long-lived and retain their tumor-supporting function, we developed a transplantation mouse model and performed lineage-tracing.
Results:
We discovered that macrophages can survive transplantation and stay present in the tumor much longer than previously suggested, while sustaining an M2-polarized protumorigenic phenotype. Transplanted tumors showed a more aggressive growth and faster polarization of the TAMs toward an M2 phenotype compared with primary tumors, a process dependent on the presence of few cotransplanted macrophages.
Conclusions:
Overall, we propose a new way for tumor-educated TAMs to contribute to glioma aggressiveness by long survival and stable protumorigenic features. These properties could have a relapse-supporting effect.
Insights
Tumor-associated macrophages (TAMs) can survive long-term in the brain after glioma removal, maintaining a tumor-promoting M2 state. This long survival and stable protumorigenic function may drive glioma aggressiveness and relapse.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Biology
Background:
- The tumor microenvironment significantly supports glioma progression.
- Tumor-associated macrophages (TAMs), particularly M2-polarized ones, are prevalent in advanced glioma and contribute to tumor growth, invasion, and angiogenesis.
- The role of M2 TAMs in glioma relapse remains under investigation.
Purpose of the Study:
- To determine if tumor-educated stromal cells, including TAMs, persist after primary tumor resection and retain tumor-supportive capabilities.
- To investigate the long-term behavior and function of TAMs in the context of glioma recurrence.
Main Methods:
- Development of a mouse transplantation model for studying residual stromal cells.
- Utilizing lineage-tracing techniques to track macrophage survival and phenotype.
- Comparative analysis of primary and transplanted tumors for growth dynamics and TAM polarization.
Main Results:
- Macrophages demonstrate extended survival within the tumor microenvironment post-transplantation, longer than previously thought.
- Sustained M2-polarized, protumorigenic phenotype in surviving macrophages.
- Transplanted tumors exhibited accelerated growth and enhanced TAM M2 polarization, dependent on cotransplanted macrophages.
Conclusions:
- Tumor-educated TAMs can contribute to glioma aggressiveness through prolonged survival and stable protumorigenic characteristics.
- These persistent TAM properties represent a novel mechanism potentially promoting tumor relapse.
- Findings suggest TAMs as a therapeutic target to prevent glioma recurrence.
