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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 3/2014

01-03-2014 | Original Article

Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab

Authors: Christiane Meyer, Laurène Cagnon, Carla M. Costa-Nunes, Petra Baumgaertner, Nicole Montandon, Loredana Leyvraz, Olivier Michielin, Emanuela Romano, Daniel E. Speiser

Published in: Cancer Immunology, Immunotherapy | Issue 3/2014

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Abstract

Metastatic melanoma has a poor prognosis with high resistance to chemotherapy and radiation. Recently, the anti-CTLA-4 antibody ipilimumab has demonstrated clinical efficacy, being the first agent to significantly prolong the overall survival of inoperable stage III/IV melanoma patients. A major aim of patient immune monitoring is the identification of biomarkers that predict clinical outcome. We studied circulating myeloid-derived suppressor cells (MDSC) in ipilimumab-treated patients to detect alterations in the myeloid cell compartment and possible correlations with clinical outcome. Lin− CD14+ HLA-DR− monocytic MDSC were enriched in peripheral blood of melanoma patients compared to healthy donors (HD). Tumor resection did not significantly alter MDSC frequencies. During ipilimumab treatment, MDSC frequencies did not change significantly compared to baseline levels. We observed high inter-patient differences. MDSC frequencies in ipilimumab-treated patients were independent of baseline serum lactate dehydrogenase levels but tended to increase in patients with severe metastatic disease (M1c) compared to patients with metastases in skin or lymph nodes only (M1a), who had frequencies comparable to HD. Interestingly, clinical responders to ipilimumab therapy showed significantly less lin− CD14+ HLA-DR− cells as compared to non-responders. The data suggest that the frequency of monocytic MDSC may be used as predictive marker of response, as low frequencies identify patients more likely benefitting from ipilimumab treatment. Prospective clinical trials assessing MDSC frequencies as potential biomarkers are warranted to validate these observations.
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Metadata
Title
Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab
Authors
Christiane Meyer
Laurène Cagnon
Carla M. Costa-Nunes
Petra Baumgaertner
Nicole Montandon
Loredana Leyvraz
Olivier Michielin
Emanuela Romano
Daniel E. Speiser
Publication date
01-03-2014
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 3/2014
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-013-1508-5

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