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000120518 1001_ $$ade Coaña, Yago Pico$$b0
000120518 245__ $$aIpilimumab treatment decreases monocytic MDSCs and increases CD8 effector memory T cells in long-term survivors with advanced melanoma.
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000120518 520__ $$aIpilimumab has revolutionized malignant melanoma therapy, but a better understanding of the mechanisms behind treatment response and adverse effects is needed. In this work, the immune system of ipilimumab treated patients was monitored to investigate potential mechanisms of action that may correlate with treatment outcome. Blood samples from 43 advanced melanoma patients were taken before, during and at the end of treatment. Hematological parameters were measured and flow cytometry analysis was performed in fresh samples within two hours of sample collection. Strong differences in markers CD45RA, CCR7, HLA-DR and CD15 between fresh and cryopreserved samples were observed. Ipilimumab treatment increased absolute lymphocyte counts, eosinophils, effector T cells and their activation status, whilst diminishing the suppressive side of the immune response, acting on regulatory T cells and myeloid derived suppressor cells (MDSCs). These effects were visible after one ipilimumab infusion and, regarding eosinophil counts, correlated with onset of adverse events. Monocytic MDSCs were decreased in response to treatment only in patients with clinical benefit; additionally, patients with a lower frequency of these cells after the first ipilimumab infusion experienced increased overall survival. CD8 effector memory T cell frequencies at the end of treatment were higher in patients with clinical benefit and positively correlated with survival. These data show that a clinical response to ipilimumab not only requires reshaping T cell populations, but additionally involves a reduction in suppressive cells such as monocytic MDSCs. Our work could provide insight on predicting treatment outcome, assisting clinicians in offering the best personalized therapeutic approach.
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000120518 7001_ $$aWolodarski, Maria$$b1
000120518 7001_ $$0P:(DE-He78)e9c55f46b4b06cf835834ee7e3e00db8$$aPoschke, Isabel$$b2$$udkfz
000120518 7001_ $$aYoshimoto, Yuya$$b3
000120518 7001_ $$aYang, Yuan$$b4
000120518 7001_ $$aNyström, Maria$$b5
000120518 7001_ $$aEdbäck, Ulrika$$b6
000120518 7001_ $$aBrage, Suzanne Eghyazi$$b7
000120518 7001_ $$aLundqvist, Andreas$$b8
000120518 7001_ $$aMasucci, Giuseppe V$$b9
000120518 7001_ $$aHansson, Johan$$b10
000120518 7001_ $$aKiessling, Rolf$$b11
000120518 773__ $$0PERI:(DE-600)2560162-3$$a10.18632/oncotarget.15368$$gVol. 8, no. 13$$n13$$p21539-21553$$tOncoTarget$$v8$$x1949-2553$$y2017
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000120518 9141_ $$y2017
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