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000126575 0247_ $$2doi$$a10.1158/1078-0432.CCR-15-0676
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000126575 1001_ $$0P:(DE-He78)d239d6a28875058b40c13266babadb58$$aGebhardt, Christoffer$$b0$$eFirst author$$udkfz
000126575 245__ $$aMyeloid Cells and Related Chronic Inflammatory Factors as Novel Predictive Markers in Melanoma Treatment with Ipilimumab.
000126575 260__ $$aPhiladelphia, Pa. [u.a.]$$bAACR$$c2015
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000126575 520__ $$aImmunotherapy 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.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.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.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.
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000126575 650_7 $$2NLM Chemicals$$aAntibodies, Monoclonal
000126575 650_7 $$2NLM Chemicals$$aAntineoplastic Agents
000126575 650_7 $$2NLM Chemicals$$aBiomarkers
000126575 650_7 $$2NLM Chemicals$$aInflammation Mediators
000126575 650_7 $$06T8C155666$$2NLM Chemicals$$aipilimumab
000126575 7001_ $$0P:(DE-HGF)0$$aSevko, Alexandra$$b1
000126575 7001_ $$0P:(DE-HGF)0$$aJiang, Huanhuan$$b2
000126575 7001_ $$0P:(DE-HGF)0$$aLichtenberger, Ramtin$$b3
000126575 7001_ $$0P:(DE-He78)20246d15b713462495c9cec21a61c7da$$aReith, Maike$$b4$$udkfz
000126575 7001_ $$0P:(DE-He78)0acd2b06b647ba4fff149a3c0eb463bf$$aTarnanidis, Kathrin$$b5$$udkfz
000126575 7001_ $$0P:(DE-He78)457c042884c901eb0a02c18bb1d30103$$aHolland-Letz, Tim$$b6$$udkfz
000126575 7001_ $$0P:(DE-He78)d5882ffec9d5dea0104c7d33165e4a45$$aUmansky, Ludmila$$b7$$udkfz
000126575 7001_ $$0P:(DE-He78)1732377f6242a18280bc6aaa196988d1$$aBeckhove, Philipp$$b8$$udkfz
000126575 7001_ $$aSucker, Antje$$b9
000126575 7001_ $$aSchadendorf, Dirk$$b10
000126575 7001_ $$0P:(DE-He78)a229f7724466e7efadf4a1ace1ff8af3$$aUtikal, Jochen$$b11$$udkfz
000126575 7001_ $$0P:(DE-He78)38be34240daf8b47325afc7910e77f7b$$aUmansky, Viktor$$b12$$eLast author$$udkfz
000126575 773__ $$0PERI:(DE-600)2036787-9$$a10.1158/1078-0432.CCR-15-0676$$gVol. 21, no. 24, p. 5453 - 5459$$n24$$p5453 - 5459$$tClinical cancer research$$v21$$x1557-3265$$y2015
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