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: J David Peske, Elizabeth D Thompson, Lelisa Gemta, Richard A Baylis, Yang-Xin Fu, Victor H Engelhard
• Journal: Nature communications (Nat Commun) Vol. 6 Pg. 7114 (May 13 2015) ISSN: 2041-1723 [Electronic] England
• PMID: 25968334 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Chemokine CCL21
• Immunoglobulins
• Lymphotoxin beta Receptor

Topics

• Animals
• Antigens, Neoplasm
• Chemokine CCL21 (genetics, metabolism)
• Female
• Gene Expression Regulation
• Immunoglobulins
• Lymphotoxin beta Receptor (immunology)
• Mice
• Mice, Knockout
• Neoplasms, Experimental (pathology)
• T-Lymphocytes (physiology)
• Tumor Microenvironment