Media type: E-Article Title: Clinical Significance of Circulating CD33+CD11b+HLA-DR− Myeloid Cells in Patients with Stage IV Melanoma Treated with Ipilimumab Contributor: Sade-Feldman, Moshe; Kanterman, Julia; Klieger, Yair; Ish-Shalom, Eliran; Olga, Mizrahi; Saragovi, Amijai; Shtainberg, Hani; Lotem, Michal; Baniyash, Michal Published: American Association for Cancer Research (AACR), 2016 Published in: Clinical Cancer Research, 22 (2016) 23, Seite 5661-5672 Language: English DOI: 10.1158/1078-0432.ccr-15-3104 ISSN: 1078-0432; 1557-3265 Origination: University thesis: Footnote: Description: <jats:title>Abstract</jats:title> <jats:p>Purpose: High levels of circulating myeloid-derived suppressor cells (MDSCs) in various cancer types, including melanoma, were shown to correlate with poor survival. We investigated whether frequencies of circulating CD33+CD11b+HLA-DR− MDSCs could be used as immune system monitoring biomarkers to predict response and survival of patients with stage IV melanoma treated with anti-CTLA4 (ipilimumab) therapy.</jats:p> <jats:p>Experimental Design: Peripheral blood samples from 56 patients and 50 healthy donors (HDs) were analyzed for CD33+CD11b+HLA-DR− MDSC percentage, NO−, and hROS levels by flow cytometry. We determined whether MDSC levels and suppressive features detected before anti-CTLA4 therapy correlate with the patients' response and overall survival (OS).</jats:p> <jats:p>Results: Patients with melanoma had significantly higher levels of circulating CD33+CD11b+HLA-DR− MDSCs with suppressive phenotype when compared with HDs. Low levels of MDSCs before CTLA-4 therapy correlated with an objective clinical response, long-term survival, increased CD247 expression in T cells, and an improved clinical status. No predictive impact was observed for lactate dehydrogenase (LDH). Kaplan–Meier and log-rank tests performed on the 56 patients showed that the presence of more than 55.5% of circulating CD33+CD11b+ out of the HLA-DR− cells, were associated with significant short OS (P &lt; 0.003), a median of 6.5 months, in comparison with the group showing lower MDSC frequencies, with a median survival of 15.6 months.</jats:p> <jats:p>Conclusions: Our study suggests the use of CD33+CD11b+HLA-DR− cells as a predictive and prognostic biomarker in patients with stage IV melanoma treated with anti-CTLA4 therapy. This monitoring system may aid in the development of combinatorial modalities, targeting the suppressive environment in conjunction with iplimumab, toward facilitating better disease outcomes. Clin Cancer Res; 22(23); 5661–72. ©2016 AACR.</jats:p> Access State: Open Access