Effector lymphocyte-induced lymph node-like vasculature enables naïve T-cell entry into tumors and enhanced anti-tumor immunity

Abstract

The presence of lymph node (LN)-like vasculature in tumors, 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 naïve T-cells that significantly delay tumor outgrowth after intratumoral activation. Development of this vasculature is controlled by a mechanism involving effector CD8 T-cells and NK cells that secrete LTα ₃ and IFNγ. LN-like vasculature is also associated with organized aggregates of B-lymphocytes and gp38 ⁺ fibroblasts that 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-tumor immunity.