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Updated: Oct 31, 2025
In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
Turning enemies into allies-reprogramming tumor-associated macrophages for cancer therapy
Martina Molgora1, Marco Colonna1
1Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, 63110, USA.
Abstract:
Checkpoint blockade therapies that target inhibitory receptors on T cells have revolutionized clinical oncology. Antibodies targeting CTLA-4 or the PD-1/PD-L1 axis are now successfully used alone or in combination with chemotherapy for numerous tumor types. Despite the clinical success of checkpoint blockade therapies, tumors exploit multiple mechanisms to escape or subvert the anti-tumor T cell response. Within the tumor microenvironment, tumor-associated macrophages (TAM) can suppress T cell responses and facilitate tumor growth in various ways, ultimately debilitating clinical responses to T cell checkpoint inhibitors. There is therefore significant interest in identifying biologicals and drugs that target immunosuppressive TAM within the tumor microenvironment and can be combined with immune checkpoint inhibitors. Here we review approaches that are currently being evaluated to convert immunosuppressive TAM into immunostimulatory macrophages that promote T cell responses and tumor elimination. Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment that impact anti-tumor immune responses and susceptibility to checkpoint blockade. TAMs are very heterogeneous and can be either immunosuppressive or immunostimulatory. Here, Molgora and Colonna review current strategies that aim to reprogram TAMs to enhance rather than inhibit immune responses.
Insights
Checkpoint blockade therapies show promise in cancer treatment. This review explores strategies to reprogram tumor-associated macrophages (TAMs) from immunosuppressive to immunostimulatory, enhancing anti-tumor T cell responses and improving immunotherapy efficacy.
Area of Science:
- Immunology
- Oncology
- Cancer Biology
Background:
- Checkpoint blockade therapies targeting CTLA-4 and PD-1/PD-L1 have transformed cancer treatment.
- Tumors employ mechanisms to evade T cell responses, with tumor-associated macrophages (TAMs) playing a key role in suppressing anti-tumor immunity within the tumor microenvironment.
- The immunosuppressive function of TAMs can limit the effectiveness of current immune checkpoint inhibitors.
Purpose of the Study:
- To review current strategies aimed at reprogramming immunosuppressive TAMs into immunostimulatory macrophages.
- To explore methods for combining TAM-targeting therapies with immune checkpoint inhibitors to enhance anti-tumor responses.
- To highlight the potential of modulating TAMs to overcome tumor resistance to immunotherapy.
Main Methods:
- Review of current literature on TAM biology and therapeutic strategies.
- Analysis of approaches to convert immunosuppressive TAMs to immunostimulatory phenotypes.
- Evaluation of combination therapies involving TAM reprogramming and immune checkpoint inhibitors.
Main Results:
- TAMs are heterogeneous and critically influence the tumor microenvironment's immune status.
- Strategies are being developed to convert immunosuppressive TAMs into pro-inflammatory, anti-tumorigenic cells.
- Reprogramming TAMs holds promise for improving responses to checkpoint blockade therapies.
Conclusions:
- Modulating TAMs represents a promising therapeutic avenue to enhance anti-tumor immunity.
- Targeting TAMs can potentially overcome resistance mechanisms to immune checkpoint inhibitors.
- Further research into TAM reprogramming is crucial for advancing cancer immunotherapy.
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