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

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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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Acknowledgments

We are obliged to the patients and blood donors for their dedicated collaboration. We thank Maurice Matter, Laurence de Leval, Ivan Letovanec, Pu Yan, Gregoire Berthod, Stephane Badel, Hasna Bouchaab, Guillaume Buss, Alexandre Christinat, Florian Claude, Nathalie Divorne, Mauro Figeri, Mathilde Gavillet, Athina Stravodimou, Donatienne Taylor, Evangelia Tzika, Jean-Philippe Zuercher, Pedro Romero, Nathalie Rufer, Laurent Derré, Samia Abed-Maillard, Lukas Baitsch, Natacha Bordry, Marion Braun, Silvia Fuertes-Marraco, Philippe Gannon, Bhawna Gupta, Michaël Hebeisen, Agnès Hiou, Marina Iancu, Kalliopi Ioannidou, Camilla Jandus, Danny Labes, Luc Lebon, Amandine Legat, Tanja Lövgren, Alexandra Michel, Faiza Mourali-Ayari, Timothy Murray, Natalie Neubert, Eran Ophir, Danilo Presotto, Jean-Paul Rivals, Godehard Scholz, Alexandre Wicky and Sintia Winkler for collaboration and advice and Martine van Overloop for administrative assistance. We thank Mohamed Faouzi and Pierluigi Ballabeni for help with statistics. This work was supported by Ludwig Cancer Research, the Cancer Vaccine Collaborative, the CRI (all NY, USA), the ISREC Foundation, the Swiss National Science Foundation (310030_135553 and CRSII3_141879), and the Swiss Cancer League (02836-08-2011).

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Authors and Affiliations

  1. Ludwig Center for Cancer Research of the University of Lausanne, Lausanne, Switzerland

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

  2. Service of Medical Oncology, Department of Oncology, Lausanne University Hospital Center (CHUV), Lausanne, Switzerland

    Olivier Michielin, Emanuela Romano & Daniel E. Speiser

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  1. Christiane Meyer
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  2. Laurène Cagnon
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Correspondence to Daniel E. Speiser.

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Meyer, C., Cagnon, L., Costa-Nunes, C.M. et al. Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol Immunother 63, 247–257 (2014). https://doi.org/10.1007/s00262-013-1508-5

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