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

Details

Serval ID
serval:BIB_9606B044F312
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab.
Journal
Cancer Immunology, Immunotherapy : Cii
Author(s)
Meyer C., Cagnon L., Costa-Nunes C.M., Baumgaertner P., Montandon N., Leyvraz L., Michielin O., Romano E., Speiser D.E.
ISSN
1432-0851 (Electronic)
ISSN-L
0340-7004
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
63
Number
3
Pages
247-257
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
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.
Keywords
Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal/administration & dosage, Antigens, CD14/metabolism, Biomarkers, Pharmacological, Cell Count, Female, Humans, Immune Tolerance, Male, Melanoma/blood, Melanoma/drug therapy, Middle Aged, Myeloid Cells/drug effects, Myeloid Cells/immunology, Neoplasm Metastasis, Neoplasm Staging, Skin Neoplasms/blood, Skin Neoplasms/drug therapy, Treatment Outcome, Young Adult
Pubmed
Web of science
Create date
10/09/2014 8:41
Last modification date
01/04/2020 13:59
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