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research article

Tumor lymphangiogenesis promotes T cell infiltration and potentiates immunotherapy in melanoma

Fankhauser, Manuel
•
Broggi, Maria A. S.
•
Potin, Lambert
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2017
Science Translational Medicine

In melanoma, vascular endothelial growth factor-C (VEGF-C) expression and consequent lymphangiogenesis correlate with metastasis and poor prognosis. VEGF-C also promotes tumor immunosuppression, suggesting that lymphangiogenesis inhibitors may be clinically useful in combination with immunotherapy. We addressed this concept in mouse melanoma models with VEGF receptor-3 (VEGFR-3)-blocking antibodies and unexpectedly found that VEGF-C signaling enhanced rather than suppressed the response to immunotherapy. We further found that this effect was mediated by VEGF-C-induced CCL21 and tumor infiltration of naive T cells before immunotherapy because CCR7 blockade reversed the potentiating effects of VEGF-C. In human metastatic melanoma, gene expression of VEGF-C strongly correlated with CCL21 and T cell inflammation, and serum VEGF-C concentrations associated with both T cell activation and expansion after peptide vaccination and clinical response to checkpoint blockade. We propose that VEGF-C potentiates immunotherapy by attracting naive T cells, which are locally activated upon immunotherapy-induced tumor cell killing, and that serum VEGF-C may serve as a predictive biomarker for immunotherapy response.

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Type
research article
DOI
10.1126/scitranslmed.aal4712
Web of Science ID

WOS:000410560500003

Author(s)
Fankhauser, Manuel
Broggi, Maria A. S.
Potin, Lambert
Bordry, Natacha
Jeanbart, Laura
Lund, Amanda W.
Da Costa, Elodie
Hauert, Sylvie
Rincon-Restrepo, Marcela
Tremblay, Christopher
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Date Issued

2017

Publisher

Amer Assoc Advancement Science

Published in
Science Translational Medicine
Volume

9

Issue

407

Article Number

eaal4712

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LLCB  
Available on Infoscience
October 9, 2017
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/141191
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