研究发现，肿瘤相关巨噬细胞（TAMs）在淋巴结转移瘤中富集，促进肿瘤血管生成和转移。TAMs与正常或炎症巨噬细胞的区分标志物较少。通过对转移性淋巴结（MLNs）中TAMs的基因表达分析，揭示TAMs高表达免疫抑制因子和促血管生成因子。特别是，TIE2/CD31阳性的巨噬细胞在TAMs中占主导地位，并且在人类乳腺癌转移性淋巴结中高度浸润，但不在反应性增生淋巴结中。因此，TIE2/CD31巨噬细胞可能成为临床诊断肿瘤转移的独特病理生物标志物，同时也是TAMs特异性癌症治疗的新靶点。
摘要：
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. However, 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. Furthermore, we isolated pure populations of TAMs from MLNs and characterized their gene expression signatures compared to peritoneal macrophages (PMs), and found that TAMs significantly overexpress immunosuppressive cytokines such as IL-4, IL-10, and TGF-β as well as proangiogenic factors such as VEGF, TIE2, and CD31. Notably, immunological analysis revealed that TIE2/CD31macrophages constitute the predominant population of TAMs that infiltrate MLNs, distinct from tissue or inflammatory macrophages. Importantly, these TIE2/CD31macrophages also heavily infiltrated MLNs from human breast cancer biopsies but not reactive hyperplastic LNs. Thus, TIE2/CD31macrophages may be a unique histopathological biomarker for detecting metastasis in clinical diagnosis, and a novel and promising target for TAM-specific cancer therapy.
展开
扫一扫
被折叠的 条评论
为什么被折叠?
到【灌水乐园】发言
