Cancer Immunology, Immunotherapy

, Volume 63, Issue 3, pp 247–257 | Cite as

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

  • Christiane Meyer
  • Laurène Cagnon
  • Carla M. Costa-Nunes
  • Petra Baumgaertner
  • Nicole Montandon
  • Loredana Leyvraz
  • Olivier Michielin
  • Emanuela Romano
  • Daniel E. Speiser
Original Article

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

MDSC Ipilimumab CTLA-4 Melanoma 

Supplementary material

262_2013_1508_MOESM1_ESM.pdf (810 kb)
Supplementary material 1 (PDF 810 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Christiane Meyer
    • 1
  • Laurène Cagnon
    • 1
  • Carla M. Costa-Nunes
    • 1
  • Petra Baumgaertner
    • 1
  • Nicole Montandon
    • 1
  • Loredana Leyvraz
    • 1
  • Olivier Michielin
    • 1
    • 2
  • Emanuela Romano
    • 2
  • Daniel E. Speiser
    • 1
    • 2
  1. 1.Ludwig Center for Cancer Research of the University of LausanneLausanneSwitzerland
  2. 2.Service of Medical Oncology, Department of OncologyLausanne University Hospital Center (CHUV)LausanneSwitzerland

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