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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 7/2012

Open Access 01-07-2012 | Original article

The chemotherapeutic drug oxaliplatin differentially affects blood DC function dependent on environmental cues

Authors: Jurjen Tel, Stanleyson V. Hato, Ruurd Torensma, Sonja I. Buschow, Carl G. Figdor, W. Joost Lesterhuis, I. Jolanda M. de Vries

Published in: Cancer Immunology, Immunotherapy | Issue 7/2012

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Abstract

It has become evident that the tumor microenvironment plays a pivotal role in the maintenance of cancerous growth. One of the acquired functions of the tumor microenvironment is the suppression of immune responses. Indeed, blocking the inhibitory pathways operational in the microenvironment results in enhanced T-cell-dependent, anti-tumor immunity. Chemotherapeutic drugs not only directly kill tumor cells but also shape the tumor microenvironment and potentiate anti-tumor immunity. Here, we demonstrate that the chemotherapeutic compound oxaliplatin acts as a double-edged sword. Besides killing tumor cells, oxaliplatin bolsters immunosuppressive pathways, resulting in decreased activation of T cells by human plasmacytoid dendritic cells (pDCs). Exposure to oxaliplatin markedly increased expression of the T-cell inhibitory molecule programmed death receptor-ligand 1 (PD-L1) on human pDCs and also TLR9-induced IFNα secretion. Furthermore, oxaliplatin decreased TLR-induced STAT1 and STAT3 expression, and NF-κB-mediated responses. The oxaliplatin induced upregulation of PD-L1 and downregulation of costimulatory molecules CD80 and CD86 resulted in decreased T-cell proliferation. Our results demonstrate that platinum-based anticancer drugs adapt TLR-induced signaling in human pDCs and myeloid DCs (mDCs), thereby downgrading their immunostimulatory potential.
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Metadata
Title
The chemotherapeutic drug oxaliplatin differentially affects blood DC function dependent on environmental cues
Authors
Jurjen Tel
Stanleyson V. Hato
Ruurd Torensma
Sonja I. Buschow
Carl G. Figdor
W. Joost Lesterhuis
I. Jolanda M. de Vries
Publication date
01-07-2012
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 7/2012
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-011-1189-x

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