EGF receptor (EGFR) in tumor cellsMacrophages contribute to immune responses through possessing phenotypic plasticity. Classically activated macrophages (M1 polarization) are driven by IFN-␥ and pathogenderived signals, such as LPS-activated canonical interferon-regulatory factor-3 (IRF-3) and STAT1 pathways. Macrophages with M1 polarization are characterized by production of proinflammatory cytokines and NOS2 (1). Alternatively activated macrophages (M2 polarization) are elicited by IL-4-and IL-13-activated STAT6 and IL-10-activated STAT3 signals. M2-polarized macrophages exhibit increased transcription of genes, including arginase 1 (Arg1), 4 mannose receptor 1 (Mrc1), resistin-like ␣ (Retnla, Fizz1), and chitinase 3-like 3 factor (Chi3l3, YM1) (1) and possess functions of antiinflammation, angiogenesis, and tissue repair, thus having tumor-promoting properties (1, 2). In addition, other transcriptional factors, such as NF-B (3) and IL-4-induced epigenetic changes (4) have been found to participate in directing polarization in macrophages.Tumor-associated macrophages (TAMs) in the tumor microenvironment usually exhibit M2 polarization in human and mouse models of cancers (5, 6) and possess pro-tumorigenic activities in most cancers, including promoting tumor cell proliferation, migration, and invasion, increasing angiogenesis, and suppressing immunity through secretion of growth factors such as HB-EGF, EGF, CSF-1, VEGF, and PDGF, enzymes, including metalloproteinases (MMPs), and cytokines, such as IL-6, IL-10, and TNF (7). Clinical studies have revealed that * This work was supported, in whole or in part, by National Institutes of Health Grants R01DK081134 (to F. Y.) and R01DK56008 and R01DK54993 (to D. B. P.), and core services were performed through Vanderbilt University Medical Center's Digestive Disease Research Center supported by National Institutes of Health Grant P30DK058404. This work was also supported by National Natural Science Foundation of China Grant 31471341 (to H. L.)The authors declare no conflict of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 4 The abbreviations used are: Arg1, arginase 1; TAM, tumor-associated macrophage; MMP, metalloproteinase; EGFR, EGF receptor; EMT, epithelial-mesenchymal transition; SOCS1, suppressor of cytokine signaling 1; IMCE, Immorto-Min colonic epithelial.