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Updated: Jul 28, 2026
In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
Antitumor strategies targeting macrophages: the importance of considering the differences in
Marine Monnier1,2, Léa Paolini1,2, Emeline Vinatier1,2,3
1Univ Angers, Nantes Université, Inserm, CNRS, CRCI2NA, LabEx IGO, Angers, France.
Abstract:
Macrophages are the immune cells that accumulate the most in the majority of established tumors and this accumulation is associated with a poor prognosis. Tumor-associated macrophages (TAMs) produce inflammatory cytokines and growth factors that promote tumor expansion and metastasis. TAMs have recently emerged as targets of choice to restore an efficient antitumor response and to limit tumor growth. Many molecules targeting TAMs are actually evaluated in clinical trials, alone or in combination. While these molecules induce tumor regression and stimulate cytotoxic responses in mouse models of tumor development, results from early clinical trials are less impressive. In this review, we list the biological differences between human and mouse macrophages that help explain the different efficacy of antitumor strategies targeting TAMs between human and animal studies. Differences in the impact of survival and polarization factors and in the cytokines produced and markers expressed as well as the limitations of extrapolations based on in vitro models of TAM-like generation should be considered in order to improve the design and efficacy of antitumor drugs targeting TAMs.
Insights
Tumor-associated macrophages (TAMs) are key in cancer but treatments effective in mice fail in humans. Biological differences between human and mouse macrophages explain this discrepancy, guiding better drug development.
Area of Science:
- Immunology
- Oncology
- Translational Medicine
Background:
- Macrophages are the most abundant immune cells in established tumors, correlating with poor prognosis.
- Tumor-associated macrophages (TAMs) promote tumor growth and metastasis via cytokines and growth factors.
Purpose of the Study:
- To review biological differences between human and mouse macrophages.
- To explain the varying efficacy of TAM-targeting antitumor strategies in human versus animal studies.
- To inform the design of more effective TAM-targeting drugs.
Main Methods:
- Literature review focusing on comparative immunology and oncology.
- Analysis of factors influencing macrophage survival and polarization.
- Examination of cytokine production and marker expression differences.
Main Results:
- Significant biological disparities exist between human and mouse macrophages.
- Differences in survival factors, polarization, cytokines, and markers impact treatment efficacy.
- In vitro models of TAM-like cells have limitations in predicting in vivo responses.
Conclusions:
- Understanding human-mouse macrophage differences is crucial for successful TAM-targeted therapies.
- Improved drug design requires consideration of these biological variations.
- Bridging the gap between preclinical models and clinical outcomes is essential for advancing cancer treatment.
