Ipilimumab treatment decreases monocytic MDSCs and increases CD8 effector memory T cells in long-term survivors with advanced melanoma
Yago Pico de Coaña1*, Maria Wolodarski1, Isabel Poschke2, Yuya Yoshimoto3, Yuan Yang1, Maria Nyström1, Suzanne Eghyazi Brage1, Andreas Lundqvist1, Giuseppe V. Masucci1, Johan Hansson1, Rolf Kiessling1
1Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; 2Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center, Heidelberg, Germany; 3Department of Radiation Oncology, Gunma University Graduate School of Medicine
Ipilimumab has revolutionized malignant melanoma therapy, but a better understanding of the mechanisms behind treatment response and adverse effects is needed. We monitored the immune system of ipilimumab treated patients 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. 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 effector T cells and their activation status, whilst diminishing the suppressive side of the immune response, acting on regulatory T cells and MDSCs. These effects were visible after one ipilimumab infusion. 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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