Peske J David, Thompson Elizabeth D, Gemta Lelisa, Baylis Richard A, Fu Yang-Xin, Engelhard Victor H
Department of Microbiology and Carter Immunology Center, University of Virginia School of Medicine, Box 801386, Charlottesville, Virginia 22901, USA.
Department of Pathology and Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA.
Nat Commun. 2015 May 13;6:7114. doi: 10.1038/ncomms8114.
The presence of lymph node (LN)-like vasculature in tumours, characterized by expression of peripheral node addressin and chemokine CCL21, is correlated with T-cell infiltration and positive prognosis in breast cancer and melanoma patients. However, mechanisms controlling the development of LN-like vasculature and how it might contribute to a beneficial outcome for cancer patients are unknown. Here we demonstrate that LN-like vasculature is present in murine models of melanoma and lung carcinoma. It enables infiltration by naive T cells that significantly delay tumour outgrowth after intratumoral activation. Development of this vasculature is controlled by a mechanism involving effector CD8 T cells and NK cells that secrete LTα3 and IFNγ. LN-like vasculature is also associated with organized aggregates of B lymphocytes and gp38(+) fibroblasts, which resemble tertiary lymphoid organs that develop in models of chronic inflammation. These results establish LN-like vasculature as both a consequence of and key contributor to anti-tumour immunity.
肿瘤中存在以外周淋巴结地址素和趋化因子CCL21表达为特征的淋巴结（LN）样脉管系统，这与乳腺癌和黑色素瘤患者的T细胞浸润及良好预后相关。然而，控制LN样脉管系统发育的机制以及它如何为癌症患者带来有益结果尚不清楚。在此，我们证明在黑色素瘤和肺癌的小鼠模型中存在LN样脉管系统。它能使幼稚T细胞浸润，这些T细胞在肿瘤内激活后能显著延迟肿瘤生长。这种脉管系统的发育受一种涉及分泌LTα3和IFNγ的效应性CD8 T细胞和NK细胞的机制控制。LN样脉管系统还与B淋巴细胞和gp38(+)成纤维细胞的有组织聚集体相关，这些聚集体类似于在慢性炎症模型中发育的三级淋巴器官。这些结果确立了LN样脉管系统既是抗肿瘤免疫的结果又是其关键促成因素。
