Melanoma-conditioned medium promotes cytotoxic immune responses by murine bone marrow-derived monocytes despite their expression of ‘M2’ markers

Macrophages have been shown to infiltrate a wide range of malignancies and are often considered to promote tumour survival, growth and spread. However, the source and behaviour of discrete tumour-associated macrophage populations are still poorly understood. Here we show a novel method for the rational development of bone marrow-derived monocytes appropriate for the study of processes which involve the contribution of circulating inflammatory monocytes. We have shown that in response to tumour-conditioned medium, these cells upregulate CD206 and CD115, markers traditionally associated with M2-type macrophages. Treated cells show reduced capacity for cytokine secretion but significantly impact CD4⁺ and CD8⁺ T-cell proliferation and polarization. Coculture with conditioned bone marrow-derived monocytes significantly reduced CD4⁺ T-cell proliferation but increased CD8⁺ T-cell proliferation and granzyme B expression with significant induction of IFNγ secretion by both CD4⁺ and CD8⁺ T cells, indicating that these cells may have a role in promoting anti-cancer immunity.