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

Amanda 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

146 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Cross-Priming
Vascular Endothelial Growth Factor C
Immune Tolerance
Experimental Melanomas
Neoplasm Antigens
Tumors
Lymph Nodes
T-cells
Endothelial cells
Neoplasms
Endothelial Cells
T-Lymphocytes
Immunity
Bearings (structural)
Lymphatic Endothelium
Antigens
Immunomodulation
Immune system
Immune System
Melanoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Lund, A., Duraes, F. V., Hirosue, S., Raghavan, V. R., Nembrini, C., Thomas, S. N., ... Swartz, M. A. (2012). VEGF-C Promotes Immune Tolerance in B16 Melanomas and Cross-Presentation of Tumor Antigen by Lymph Node Lymphatics. Cell Reports, 1(3), 191-199. https://doi.org/10.1016/j.celrep.2012.01.005

VEGF-C Promotes Immune Tolerance in B16 Melanomas and Cross-Presentation of Tumor Antigen by Lymph Node Lymphatics. / Lund, Amanda; Duraes, Fernanda V.; Hirosue, Sachiko; Raghavan, Vidya R.; Nembrini, Chiara; Thomas, Susan N.; Issa, Amine; Hugues, Stéphanie; Swartz, Melody A.

In: Cell Reports, Vol. 1, No. 3, 29.03.2012, p. 191-199.

Research output: Contribution to journalArticle

Lund, A, Duraes, FV, Hirosue, S, Raghavan, VR, Nembrini, C, Thomas, SN, Issa, A, Hugues, S & Swartz, MA 2012, 'VEGF-C Promotes Immune Tolerance in B16 Melanomas and Cross-Presentation of Tumor Antigen by Lymph Node Lymphatics', Cell Reports, vol. 1, no. 3, pp. 191-199. https://doi.org/10.1016/j.celrep.2012.01.005
Lund, Amanda ; Duraes, Fernanda V. ; Hirosue, Sachiko ; Raghavan, Vidya R. ; Nembrini, Chiara ; Thomas, Susan N. ; Issa, Amine ; Hugues, Stéphanie ; Swartz, Melody A. / VEGF-C Promotes Immune Tolerance in B16 Melanomas and Cross-Presentation of Tumor Antigen by Lymph Node Lymphatics. In: Cell Reports. 2012 ; Vol. 1, No. 3. pp. 191-199.
@article{3fc1d970c5f940b085d207e2aa396edc,
title = "VEGF-C Promotes Immune Tolerance in B16 Melanomas and Cross-Presentation of Tumor Antigen by Lymph Node Lymphatics",
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.",
author = "Amanda Lund and Duraes, {Fernanda V.} and Sachiko Hirosue and Raghavan, {Vidya R.} and Chiara Nembrini and Thomas, {Susan N.} and Amine Issa and St{\'e}phanie Hugues and Swartz, {Melody A.}",
year = "2012",
month = "3",
day = "29",
doi = "10.1016/j.celrep.2012.01.005",
language = "English (US)",
volume = "1",
pages = "191--199",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - VEGF-C Promotes Immune Tolerance in B16 Melanomas and Cross-Presentation of Tumor Antigen by Lymph Node Lymphatics

AU - Lund, Amanda

AU - Duraes, Fernanda V.

AU - Hirosue, Sachiko

AU - Raghavan, Vidya R.

AU - Nembrini, Chiara

AU - Thomas, Susan N.

AU - Issa, Amine

AU - Hugues, Stéphanie

AU - Swartz, Melody A.

PY - 2012/3/29

Y1 - 2012/3/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84861116064&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861116064&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2012.01.005

DO - 10.1016/j.celrep.2012.01.005

M3 - Article

VL - 1

SP - 191

EP - 199

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 3

ER -