title: Effector lymphocyte-induced lymph node-like vasculature enables naive T-cell entry into tumours and enhanced anti-tumour immunity.
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.
authors.affiliation: Department of Microbiology and Carter Immunology Center, University of Virginia School of Medicine, Box 801386, Charlottesville, Virginia 22901, USA.
authors.forename: J David
authors.initials: JD
authors.lastname: Peske
authors.affiliation: Department of Microbiology and Carter Immunology Center, University of Virginia School of Medicine, Box 801386, Charlottesville, Virginia 22901, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Thompson
authors.affiliation: Department of Microbiology and Carter Immunology Center, University of Virginia School of Medicine, Box 801386, Charlottesville, Virginia 22901, USA.
authors.forename: Lelisa
authors.initials: L
authors.lastname: Gemta
authors.affiliation: Department of Microbiology and Carter Immunology Center, University of Virginia School of Medicine, Box 801386, Charlottesville, Virginia 22901, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Baylis
authors.affiliation: Department of Pathology and Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
authors.affiliation: Department of Microbiology and Carter Immunology Center, University of Virginia School of Medicine, Box 801386, Charlottesville, Virginia 22901, USA.
authors.forename: Victor H
authors.initials: VH
authors.lastname: Engelhard
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm; D054421:Chemokine CCL21 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D007136:Immunoglobulins; D053259:Lymphotoxin beta Receptor / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000473:pathology*; D013601:T-Lymphocytes / Q000502:physiology*; D059016:Tumor Microenvironment
chemical_list: D000951:Antigens, Neoplasm; D054421:Chemokine CCL21; D007136:Immunoglobulins; D053259:Lymphotoxin beta Receptor