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

JD Peske, ED Thompson, L Gemta, RA Baylis… - Nature …, 2015 - nature.com
JD Peske, ED Thompson, L Gemta, RA Baylis, YX Fu, VH Engelhard
Nature communications, 2015nature.com
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 …
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.
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