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research article

Lymphatic vessels regulate immune microenvironments in human and murine melanoma

Lund, Amanda W.
•
Wagner, Marek
•
Fankhauser, Manuel
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2016
Journal Of Clinical Investigation

Lymphatic remodeling in tumor microenvironments correlates with progression and metastasis, and local lymphatic vessels play complex and poorly understood roles in tumor immunity. Tumor lymphangiogenesis is associated with increased immune suppression, yet lymphatic vessels are required for fluid drainage and immune cell trafficking to lymph nodes, where adaptive immune responses are mounted. Here, we examined the contribution of lymphatic drainage to tumor inflammation and immunity using a mouse model that lacks dermal lymphatic vessels (K14-VEGFR3-Ig mice). Melanomas implanted in these mice grew robustly, but exhibited drastically reduced cytokine expression and leukocyte infiltration compared with those implanted in control animals. In the absence of local immune suppression, transferred cytotoxic T cells more effectively controlled tumors in K14-VEGFR3-Ig mice than in control mice. Furthermore, gene expression analysis of human melanoma samples revealed that patient immune parameters are markedly stratified by levels of lymphatic markers. This work suggests that the establishment of tumor-associated inflammation and immunity critically depends on lymphatic vessel remodeling and drainage. Moreover, these results have implications for immunotherapies, the efficacies of which are regulated by the tumor immune microenvironment.

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Type
research article
DOI
10.1172/Jci79434
Web of Science ID

WOS:000382513400021

Author(s)
Lund, Amanda W.
Wagner, Marek
Fankhauser, Manuel
Steinskog, Eli S.
Broggi, Maria A.
Sprenger, Stefani
Gajewski, Thomas F.
Alitalo, Kari
Eikesdal, Hans P.
Wiig, Helge
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Date Issued

2016

Publisher

Amer Soc Clinical Investigation Inc

Published in
Journal Of Clinical Investigation
Volume

126

Issue

9

Start page

3389

End page

3402

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LLCB  
Available on Infoscience
October 18, 2016
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/130264
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