Myeloid cells and related chronic inflammatory factors as novel predictive markers in melanoma treatment with ipilimumab

• Verfasst von: Gebhardt, Christoffer [VerfasserIn]
• Verfasst von: Utikal, Jochen [VerfasserIn]
• Verfasst von: Umansky, Viktor [VerfasserIn]
• Titel: Myeloid cells and related chronic inflammatory factors as novel predictive markers in melanoma treatment with ipilimumab
• Verf.angabe: Christoffer Gebhardt, Alexandra Sevko, Huanhuan Jiang, Ramtin Lichtenberger, Maike Reith, Kathrin Tarnanidis, Tim Holland-Letz, Ludmila Umansky, Philipp Beckhove, Antje Sucker, Dirk Schadendorf, Jochen Utikal, and Viktor Umansky
• E-Jahr: 2015
• Jahr: August 19, 2015
• Umfang: 7 S.
• Fussnoten: Gesehen am 07.09.2017
• Titel Quelle: Enthalten in: Clinical cancer research
• Ort Quelle: Philadelphia, Pa. [u.a.] : AACR, 1995
• Jahr Quelle: 2015
• Band/Heft Quelle: 21(2015), 24, Seite 5453-5459
• ISSN Quelle: 1557-3265
• DOI: doi:10.1158/1078-0432.CCR-15-0676
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1563305127

Abstract

Purpose: Immunotherapy with ipilimumab improves the survival of patients with metastatic melanoma. Because only around 20% of patients experience long-term benefit, reliable markers are needed to predict a clinical response. Therefore, we sought to determine if some myeloid cells and related inflammatory mediators could serve as predictive factors for the patients' response to ipilimumab. Experimental Design: We performed an analysis of myeloid cells in the peripheral blood of 59 stage IV melanoma patients before the treatment and at different time points upon the therapy using a clinical laboratory analysis and multicolor flow cytometry. In addition, the production of related inflammatory factors was evaluated by ELISA or Bio-Plex assays. Results: An early increase in eosinophil count during the treatment with ipilimumab was associated with an improved clinical response. In contrast, elevated amounts of monocytic myeloid-derived suppressor cells (moMDSC), neutrophils, and monocytes were found in nonresponders (n = 36) as compared with basal levels and with responding patients (n = 23). Moreover, in nonresponders, moMDSCs produced significantly more nitric oxide, and granulocytic MDSCs expressed higher levels of PD-L1 than these parameters at baseline and in responders, suggesting their enhanced immunosuppressive capacity. Upon the first ipilimumab infusion, nonresponders displayed elevated serum concentrations of S100A8/A9 and HMGB1 that attract and activate MDSCs. Conclusions: These findings highlight additional mechanisms of ipilimumab effects and suggest levels of eosinophils, MDSCs, as well as related inflammatory factors S100A8/A9 and HMGB1 as novel complex predictive markers for patients who may benefit from the ipilimumab therapy. Clin Cancer Res; 21(24); 5453-9. ©2015 AACR.