VEGF-C Promotes Immune Tolerance in B16 Melanomas and Cross-Presentation of Tumor Antigen by Lymph Node Lymphatics

Amanda W. Lund, Fernanda V. Duraes, Sachiko Hirosue, Vidya R. Raghavan, Chiara Nembrini, Susan N. Thomas, Amine Issa, Stéphanie Hugues, Melody A. Swartz

Research output: Contribution to journalArticle

167 Scopus citations

Abstract

Tumor expression of the lymphangiogenic factor VEGF-C is correlated with metastasis and poor prognosis, and although VEGF-C enhances transport to the draining lymph node (dLN) and antigen exposure to the adaptive immune system, its role in tumor immunity remains unexplored. Here, we demonstrate that VEGF-C promotes immune tolerance in murine melanoma. In B16 F10 melanomas expressing a foreign antigen (OVA), VEGF-C protected tumors against preexisting antitumor immunity and promoted local deletion of OVA-specific CD8+ T cells. Naive OVA-specific CD8+ T cells, transferred into tumor-bearing mice, were dysfunctionally activated and apoptotic. Lymphatic endothelial cells (LECs) in dLNs cross-presented OVA, and naive LECs scavenge and cross-present OVA in vitro. Cross-presenting LECs drove the proliferation and apoptosis of OVA-specific CD8+ T cells ex vivo. Our findings introduce a tumor-promoting role for lymphatics in the tumor and dLN and suggest that lymphatic endothelium in the local microenvironment may be a target for immunomodulation.

Original languageEnglish (US)
Pages (from-to)191-199
Number of pages9
JournalCell Reports
Volume1
Issue number3
DOIs
StatePublished - Mar 29 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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