Effector lymphocyte-induced lymph node-like vasculature enables naive T-cell entry into tumours and enhanced anti-tumour immunity

J. David Peske, Elizabeth D. Thompson, Lelisa Gemta, Richard A. Baylis, Yang-Xin Fu and Victor H. Engelhard ()
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J. David Peske: University of Virginia School of Medicine, Box 801386, Charlottesville, Virginia 22901, USA
Elizabeth D. Thompson: University of Virginia School of Medicine, Box 801386, Charlottesville, Virginia 22901, USA
Lelisa Gemta: University of Virginia School of Medicine, Box 801386, Charlottesville, Virginia 22901, USA
Richard A. Baylis: University of Virginia School of Medicine, Box 801386, Charlottesville, Virginia 22901, USA
Yang-Xin Fu: University of Chicago
Victor H. Engelhard: University of Virginia School of Medicine, Box 801386, Charlottesville, Virginia 22901, USA

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms8114

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