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VEGF-C Promotes Immune Tolerance in B16 Melanomas and Cross-Presentation of Tumor Antigen by Lymph Node Lymphatics
Open accessAbstract
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.
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Citations
Cites
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Metadata
- Authors
- Lund, A. W., Duraes, F. V., Hirosue, S., Raghavan, V. R., Nembrini, C., Thomas, S. N., Issa, A., Hugues, S., & Swartz, M. A.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 1
- Issue
- 3
- Pages
- 191-199
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2016054079
- Cited by
- 341
- References
- 3
- FWCI
- 9.94
- Type
- journal article
- Language
- en
- Open access
- gold
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