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Updated: May 13, 2026
08:36
In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
Using macrophage activation to augment immunotherapy of established tumours
Z G Fridlender1, A Jassar, I Mishalian
1Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, POB 12000, Jerusalem 91120, Israel. fridlender@hadassah.org.il
British Journal of Cancer
|March 14, 2013
Summary
Altering tumor-associated macrophages (TAMs) with DMXAA enhances immunotherapy efficacy in lung cancer models. This approach reprograms the tumor microenvironment, boosting anti-tumor immune cell activity and therapeutic outcomes.
Area of Science:
- Immunology
- Cancer Research
- Drug Development
Background:
- Tumor-associated macrophages (TAMs) significantly influence the tumor microenvironment and immune suppression.
- Altering TAM phenotype is a potential strategy to enhance immunotherapy effectiveness.
Purpose of the Study:
- To investigate if modulating TAM phenotype with 5,6-Dimethylxanthenone-4-acetic-acid (DMXAA) can augment immunotherapy efficacy.
- To evaluate the impact of DMXAA on anti-tumor immune responses and the tumor microenvironment.
Main Methods:
- DMXAA was combined with active immunotherapies in murine lung cancer models.
- Anti-tumor efficacy, immune cell phenotypes (flow cytometry), and tumor microenvironment (RT-PCR) were assessed.
- Macrophage depletion was used to confirm the role of TAMs.
Main Results:
- DMXAA significantly enhanced immunotherapy effects by increasing neutrophils and M1 macrophages.
- DMXAA shifted TAM phenotypes, reduced immunosuppression, and promoted a pro-inflammatory tumor microenvironment.
- Modulating macrophages increased intratumoral CD8(+) T cell numbers, activity, and antigen-specificity.
Conclusions:
- Modulating intratumoral macrophages dramatically augmented immunotherapy effects.
- Agents that activate TAMs should be considered for future immunotherapy trials.
Related Concept Videos
01:27Tumor Immunotherapy
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
02:17The Tumor Microenvironment
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...