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

Author

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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
    Present address: Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, 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)

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.

Suggested Citation

  • J. David Peske & Elizabeth D. Thompson & Lelisa Gemta & Richard A. Baylis & Yang-Xin Fu & Victor H. Engelhard, 2015. "Effector lymphocyte-induced lymph node-like vasculature enables naive T-cell entry into tumours and enhanced anti-tumour immunity," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8114
    DOI: 10.1038/ncomms8114
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