Various other aspects of the TME have been implicated in macrophage polarization, including the presence of cancer-associated fibroblasts (CAFs)16,22, and the relative contribution of carcinoma cells vs. CAFs in eliciting this response in macrophages is not clear, nor is the mechanism through which carcinoma cells elicit the SPP1+ polarization response. The gene discussed is SPP1; the disease is carcinoma.