Interrogation and modulation of the immunosuppressive activity of human TAM-like macrophages using in vitro cultures

The tumor microenvironment (TME) supports the development of pro-tumoral macrophages. These Tumour Associated Macrophages (TAMs), resemble M2-macrophages and are characterized by an immune-suppressive phenotype. In the TME, TAMs can induce proliferation and survival of tumor cells, facilitate angiogenesis, and suppress anti-tumor immune responses via expression of co-inhibitory molecules such as PD-L1 and cytokines such as IL-10 or TGF-β1. Therefore, TAMs are a highly attractive target for innovative cancer immunotherapies. Understanding whether candidate immunotherapies can reverse TAM-mediated immune suppression or reprogram TAMs to a pro-inflammatory phenotype is key to the development of effective cancer immunotherapy. Here we outline a suite of macrophage assays that can be adopted to determine whether candidate therapeutics can reverse human M2 macrophage-mediated immune suppression and repolarise M2 macrophages.

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