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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 9/2005

01-09-2005 | Original Article

Transforming growth factor-β1 immobilises dendritic cells within skin tumours and facilitates tumour escape from the immune system

Authors: Florian Weber, Scott N. Byrne, Shery Le, David A. Brown, Samuel N. Breit, Richard A. Scolyer, Gary M. Halliday

Published in: Cancer Immunology, Immunotherapy | Issue 9/2005

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Abstract

Human skin tumours often regress spontaneously due to immune rejection. Murine skin tumours model this behaviour; some regress and others progress in syngeneic immunocompetent hosts. Previous studies have shown that progressor but not regressor skin tumours inhibit dendritic cell (DC) migration from the tumour to draining lymph nodes, and transforming growth factor-β1 (TGF-β1) has been identified as a responsible factor. To determine whether increased production of TGF-β1 in the absence of other differences inhibits DC migration from the tumour and enables it to evade immune destruction, a murine regressor squamous cell carcinoma clone was transfected with the gene for TGF-β1. This enhanced growth in vitro and in vivo, causing it to become a progressor. TGF-β1 transfection reduced the number of infiltrating DCs by about 25%. Quantitation of CD11c+ E-cadherin+ (epidermally derived) DCs in lymph nodes determined that TGF-β1 reduced the number of DCs that migrated from the tumour to undetectable levels. This was supported by showing that TGF-β1 reduced DC migration from cultured tumour explants by greater than tenfold. TGF-β1 transfection also reduced the number of infiltrating CD4 and CD8 T cells. Thus, TGF-β1 production by skin tumours is sufficient to immobilise DCs within the tumour, preventing their migration to lymph nodes. This reduces the number of T cells that infiltrate the tumour, preventing regression. Thus, TGF-β1 is a key regulator of whether skin tumours regress or progress.
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Metadata
Title
Transforming growth factor-β1 immobilises dendritic cells within skin tumours and facilitates tumour escape from the immune system
Authors
Florian Weber
Scott N. Byrne
Shery Le
David A. Brown
Samuel N. Breit
Richard A. Scolyer
Gary M. Halliday
Publication date
01-09-2005
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 9/2005
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-004-0652-3

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