Tissue-Resident Macrophages in Pancreatic Ductal Adenocarcinoma Originate from Embryonic Hematopoiesis and Promote Tumor Progression.
Tissue-Resident Macrophages in Pancreatic Ductal Adenocarcinoma Originate from Embryonic Hematopoiesis and Promote Tumor Progression.
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DOI：
10.1016/j.immuni.2017.08.018
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发表时间：
2017-09-19
期刊：
影响因子：
32.4
通讯作者：
DeNardo DG
中科院分区：
文献类型：
--
作者：
Zhu Y;Herndon JM;Sojka DK;Kim KW;Knolhoff BL;Zuo C;Cullinan DR;Luo J;Bearden AR;Lavine KJ;Yokoyama WM;Hawkins WG;Fields RC;Randolph GJ;DeNardo DG
肿瘤相关巨噬细胞（TAM）是癌症微环境的重要组成部分，在调节肿瘤进展中起着关键作用。最佳的治疗干预需要深入了解维持恶性组织中巨噬细胞的来源。在这项研究中，我们研究了TAMs在小鼠胰腺导管腺癌（PDAC）模型中的个体发生。我们确定了炎性单核细胞和组织驻留巨噬细胞作为TAM的来源。出乎意料的是，胰腺驻留巨噬细胞的显著部分起源于胚胎发育，并在肿瘤进展期间通过原位增殖而扩增。而单核细胞衍生的TAM在抗原呈递中发挥更有效的作用，胚胎衍生的TAM表现出促纤维化转录谱，表明它们在细胞外基质中产生和重塑分子的作用。总的来说，这些发现揭示了TAM起源和功能的异质性，并可以为PDAC治疗提供治疗见解。
Tumor-associated macrophages (TAMs) are essential components of the cancer microenvironment and play critical roles in the regulation of tumor progression. Optimal therapeutic intervention requires in-depth understanding of the sources that sustain macrophages in malignant tissues. In this study, we investigated the ontogeny of TAMs in murine pancreatic ductal adenocarcinoma (PDAC) models. We identified both inflammatory monocytes and tissue-resident macrophages as sources of TAMs. Unexpectedly, significant portions of pancreas-resident macrophages originated from embryonic development and expanded through in situ proliferation during tumor progression. Whereas monocyte-derived TAMs played more potent roles in antigen presentation, embryonically derived TAMs exhibited a pro-fibrotic transcriptional profile, indicative of their role in producing and remodeling molecules in the extracellular matrix. Collectively, these findings uncover the heterogeneity of TAM origin and functions and could provide therapeutic insight for PDAC treatment.
影响因子：
32.4
作者：
Zhu Y;Herndon JM;Sojka DK;Kim KW;Knolhoff BL;Zuo C;Cullinan DR;Luo J;Bearden AR;Lavine KJ;Yokoyama WM;Hawkins WG;Fields RC;Randolph GJ;DeNardo DG
通讯作者：
DeNardo DG