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

Nat Commun. 2015 May 13;6:7114. doi: 10.1038/ncomms8114.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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