Predominant Population of Tumor-Associated Macrophages Infiltrating Metastatic Lymph Nodes

Tumor-associated macrophages(TAMs) accumulate in various cancers and promote tumor angiogenesis and metastasis, and thus may be ideal targets for the clinical diagnosis of tumor metastasis with high specificity. How- ever, there are few specific markers to distinguish between TAMs and normal or inflammatory macrophages. Here, we show that TAMs localize in green fluorescent protein- labeled tumors of metastatic lymph nodes (MLNs) from B16F1 melanoma cells but not in necrotic tumor regions, suggesting that TAMs may promote the growth of tumor cells and the progression of tumor metastasis. Further- more, we isolated pure populations of TAMs from MLNs and characterized their gene expression signatures com- pared to peritoneal macrophages (PMs), and found that TAMs significantly overexpress immunosuppressive cyto- kines such as IL-4, IL-10, and TGF-β as well as proangi- ogenic factors such as VEGF, TIE2, and CD31. Notably, immunological analysis revealed that TIE2 + / CD31+ macro- phages constitute the predominant population of TAMs that infiltrate MLNs, distinct from tissue or inflammatory macrophages. Importantly, these TIE2 + / CD31+ macropha- ges also heavily infiltrated MLNs from human breast can- cer biopsies but not reactive hyperplastic LNs. Thus, TIE2 + / CD31+ macrophages may be a unique histopathological