Plasma-treated medium tunes the inflammatory profile in murine bone marrow-derived macrophages

Abstract

Purpose

Macrophages are essential drivers of tumor rejection as well as tumor promotion. Especially tumor-associated macrophages (TAM) phenotypically resemble tumor-supporting alternatively activated macrophages (M2). Targeting their phenotype has long been a matter of preclinical research in oncology. Cold physical plasma and plasma-treated medium has recently been recognized as a new possible interventional strategy in tumor treatment. Whereas several studies underlined this proof-of-concept in animal studies, it is not clear how plasma affects the phenotype of macrophages.

Methods

We differentiated macrophage from murine bone marrow-derived cells, and exposed them to plasma-treated cell culture medium. This led to a more pronounced NOS2 expression in several macrophage subtypes, a marker typically associated with a rather pro-inflammatory, antitumor phenotype. When stimulated with supernatants of pancreatic cancer cells, these macrophages released significantly increased amounts of immune-stimulatory molecules in response to plasma-treated medium. This included TNFα, IL6, IL12, CCL4, and CXCL9, whereas MCP1 and CXCL1 were significantly decreased. Interestingly, baseline expression levels as well as response to plasma-treated medium were largely opposite to macrophages stimulated with tumor cell supernatants.

Conclusion

These results call for a more differentiated view on macrophage polarization, and emphasize the immune-modulatory role that plasma-treated medium may exert in the tumor settings.