Back to Search
Start Over
Generation of monocyte-derived tumorassociated macrophages using tumorconditioned media provides a novel method to study tumor-associated macrophages in vitro.
- Source :
-
Journal for ImmunoTherapy of Cancer . 12/1/2019, Vol. 7 Issue 1, p1-14. 14p. - Publication Year :
- 2019
-
Abstract
- Background: Tumor-associated macrophages (TAM) are expanded and exhibit tumor-promoting properties within the tumor microenvironment. Current methods to study TAM have not been replicated across cancer types and often do not include exogenous growth factors from the tumor, a key factor in TAM differentiation in vivo. Methods: In this study, an in vitro method to generate monocyte- derived TAM using tumor- conditioned media (TCM) and a cytokine cocktail containing IL-4, IL-10, and M-CSF was utilized to study the phenotype, morphology, and function of TAM across multiple cancer types. TCM was generated from two breast cancer cell lines and an Epstein-Barr virus-positive lymphoma cell line. The properties of in vitro generated TAM were compared to in vitro generated M1 and M2- like macrophages and TAM isolated from patients with cancer. Results: TAM generated in this fashion displayed an increase in CD163/CD206 co-expression compared to M2- like macrophages (87 and 36%, respectively). TAM generated in vitro exhibited increased transcript levels of the functional markers IL-6, IL-10, CCL2, c-Myc, iNOS, and arginase compared to in vitro generated M2-like macrophages. Functionally, in vitro generated TAM inhibited the proliferation of T cells (47% decrease from M1-like macrophages) and the production of IFN-γ by natural killer cells was inhibited (44%) when co-cultured with TAM. Furthermore, in vitro generated TAM secreted soluble factors that promote the growth and survival of tumor cells. Conclusions: Limited access to patient TAM highlights the need for methods to generate TAM in vitro. Our data confirm that monocyte-derived TAM can be generated reliably using TCM plus the cytokine cocktail of IL-4, IL-10, and M-CSF. Given the ability of TAM to inhibit immune cell function, continued study of methods to deplete or deactivate TAM in the setting of cancer are warranted. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20511426
- Volume :
- 7
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal for ImmunoTherapy of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 164415418
- Full Text :
- https://doi.org/10.1186/s40425-019-0622-0