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Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
Differential effects of malignant mesothelioma cells on THP-1 monocytes and macrophages
Valerio Izzi1, Valerio Chiurchiù, Fabiola D'Aquilio
1Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, I-00133 Rome, Italy. valerioizzi@libero.it
Abstract:
Malignant mesothelioma (MM) is a highly fatal tumor arising from inner body membranes, whose extensive growth is facilitated by its week immunogenicity and by its ability to blunt the immune response which should arise from the huge mass of leukocytes typically infiltrating this tumor. It has been reported that the inflammatory infiltrate found in MM tissues is characterized by a high prevalence of macrophages. Thus, in this work we evaluated the ability of human MM cells to modulate the inflammatory phenotype of human THP-1 monocytes and macrophages, a widely used in vitro model of monocyte/macrophage differentiation. Furthermore, we tested the hypothesis that the exposure to MM cells could alter the differentiation of THP-1 monocytes favoring the development of alternatively activated, tumor-supporting macrophages. Our data prove for the first time that MM cells can polarize monocytes towards an altered inflammatory phenotype and macrophages towards an immunosuppressive phenotype. Moreover, we demonstrate that monocytes cocultivated with MM cells 'keep a memory' of their encounter with the tumor which influences their differentiation to macrophages. On the whole, we provide evidence that MM cells exert distinct, cell-specific effects on monocytes and macrophages. The thorough characterization of such effects may be of a crucial importance for the rational design of new immunotherapeutic protocols.
Insights
Malignant mesothelioma cells alter immune cells. These tumor cells can change monocytes into an inflammatory state and macrophages into an immunosuppressive one, impacting cancer immunity.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Malignant mesothelioma (MM) is a fatal cancer associated with impaired immune response.
- MM tumors are infiltrated by leukocytes, particularly macrophages.
- Understanding tumor-associated immune modulation is crucial for developing effective therapies.
Purpose of the Study:
- To investigate how malignant mesothelioma cells influence the inflammatory phenotype of monocytes and macrophages.
- To determine if MM cells promote the differentiation of monocytes into tumor-supporting macrophages.
- To elucidate the mechanisms by which MM cells affect immune cell function.
Main Methods:
- Utilized human THP-1 monocytes and macrophages as an in vitro model.
- Co-cultured THP-1 cells with human malignant mesothelioma cells.
- Analyzed the phenotypic and functional changes in monocytes and macrophages post-exposure to MM cells.
Main Results:
- MM cells were shown to polarize monocytes towards an altered inflammatory phenotype.
- MM cells induced macrophages to adopt an immunosuppressive phenotype.
- Monocytes exposed to MM cells retained a 'memory' that influenced their subsequent differentiation into macrophages.
Conclusions:
- Malignant mesothelioma cells exert distinct, cell-specific effects on monocyte and macrophage differentiation and function.
- MM cells actively modulate the tumor microenvironment by altering immune cell phenotypes.
- Characterizing these MM-driven immune alterations is vital for designing novel immunotherapeutic strategies against malignant mesothelioma.
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