Clinical Significance of Circulating CD33+CD11b+HLA DR Myeloid Cells in Patients with Stage IV Melanoma Treated with Ipilimumab
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. 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) 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 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. 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. (c)2016 AACR.
Clinical Cancer Research