间质细胞
重编程
肿瘤微环境
淋巴结间质细胞
趋化因子
细胞因子
癌症研究
淋巴结
免疫系统
生物
免疫学
细胞生物学
细胞
遗传学
作者
Angela Riedel,David Shorthouse,Lisa Haas,Benjamin A. Hall,Jacqueline D. Shields
出处
期刊:Nature Immunology
[Springer Nature]
日期:2016-07-11
卷期号:17 (9): 1118-1127
被引量:150
摘要
The contribution of stromal cells to the microenvironment of tumor-draining lymph nodes is poorly characterized. By comparative transcriptional analysis, Shields and colleagues find that tumors induce the stromal reprogramming of key pathways that affect the structure and function of such lymph nodes. Lymph node (LN) stromal cells, particularly fibroblastic reticular cells (FRCs), provide critical structural support and regulate immunity, tolerance and the transport properties of LNs. For many tumors, metastasis to the LNs is predictive of poor prognosis. However, the stromal contribution to the evolving microenvironment of tumor-draining LNs (TDLNs) remains poorly understood. Here we found that FRCs specifically of TDLNs proliferated in response to tumor-derived cues and that the network they formed was remodeled. Comparative transcriptional analysis of FRCs from non-draining LNs and TDLNs demonstrated reprogramming of key pathways, including matrix remodeling, chemokine and/or cytokine signaling, and immunological functions such as the recruitment, migration and activation of leukocytes. In particular, downregulation of the expression of FRC-derived chemokine CCL21 and cytokine IL-7 were accompanied by altered composition and aberrant localization of immune-cell populations. Our data indicate that following exposure to tumor-derived factors, the stroma of TDLNs adapts on multiple levels to exhibit features typically associated with immunosuppression.
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