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VEGF-C promotes immune tolerance in B16 melanomas and cross-presentation of tumor antigen by lymph node lymphatics

Lund, Amanda W
Hirosue, Sachiko
Raghavan, Vidya R
Nembrini, Chiara
Thomas, Susan N
Issa, Amine
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Published in Cell Reports. 2012, vol. 1, no. 3, p. 191-9
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.
Keywords AnimalsAntigen Presentation/immunologyAntigens, Neoplasm/immunologyApoptosis/immunologyCD8-Positive T-Lymphocytes/immunologyCancer Vaccines/immunologyCross-Priming/immunologyDendritic Cells/immunologyEndothelial Cells/metabolismHistocompatibility Antigens Class I/immunologyImmune Tolerance/immunologyLymph Nodes/immunology/pathologyLymphangiogenesisMelanoma, Experimental/immunology/pathology/prevention & controlMiceNeoplasm MetastasisPeptides/immunologyStromal Cells/metabolismVascular Endothelial Growth Factor C/metabolism
PMID: 22832193
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Research group Pathologie et immunologie (906)
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LUND, Amanda W et al. VEGF-C promotes immune tolerance in B16 melanomas and cross-presentation of tumor antigen by lymph node lymphatics. In: Cell Reports, 2012, vol. 1, n° 3, p. 191-9. doi: 10.1016/j.celrep.2012.01.005 https://archive-ouverte.unige.ch/unige:32284

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Deposited on : 2013-12-17

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