Activation of TAMs from tumor microenvironment of various tumors include hypoxia [66, 67], metabolic products of cancer cells (e.g., lactic acid) [59, 68], COX-2 [69], cytokines (e.g., TGF-β, CSF-1, GM-CSF), interleukins (IL-4, IL-10, IL-13) and plasma cells and immune complexes, damage associated molecular patterns (DAMPs), such as high-mobility group box1 protein (HMGB1), extracellular ATP, and degraded extracellular matrix components produced by cancer cells or stromal cells [70]. This evidence concerns the gene IL4 and cancer.