Tumor-macrophage crosstalk: how to listen

The tumor microenvironment contains many cellular components influencing tumor behaviors, such as metastasis, angiogenesis and chemo-resistance. Tumor-associated macrophages (TAMs) are one of such components that can also manipulate the overall prognosis and patient survival. Analysis of tumor-macrophage crosstalk is crucial as tumor cells can polarize circulatory monocytes into TAMs. Such trans-polarization of macrophages support tumor mediated evasion and suppression of immune response. Additionally, such TAMs significantly influence tumor growth and proliferation, making them a potential candidate for precision therapeutics. However, the failure of macrophage-dependent therapies at clinical trials emphasizes the fault in current perception and research modality. This review discussed this field's progress regarding emerging model systems with a focused view on the in vitro platforms. The inadequacy of currently available models and their implications on existing studies also analyzed. The need for a conceptual and experimental leap toward a human-relevant in vitro custom-built platform for studying tumor-macrophage crosstalk is acknowledged.