Clinical Significance of Circulating CD33+CD11b+HLA-DR- Myeloid Cells in Patients with Stage IV Melanoma Treated with Ipilimumab
| Autor: | Hani Shtainberg, Moshe Sade-Feldman, Michal Lotem, Yair Klieger, Michal Baniyash, Mizrahi Olga, Amijai Saragovi, Julia Kanterman, Eliran Ish-Shalom |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Oncology Male Cancer Research medicine.medical_specialty T-Lymphocytes CD33 Sialic Acid Binding Ig-like Lectin 3 Ipilimumab 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system Internal medicine Lactate dehydrogenase Biomarkers Tumor Medicine Humans Clinical significance CTLA-4 Antigen Myeloid Cells Melanoma Neoplasm Staging CD11b Antigen business.industry Cancer HLA-DR Antigens Middle Aged medicine.disease Prognosis 030104 developmental biology chemistry 030220 oncology & carcinogenesis Immunology Myeloid-derived Suppressor Cell Female business medicine.drug |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 22(23) |
| ISSN: | 1557-3265 |
| Popis: | 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. ©2016 AACR. |
| Databáze: | OpenAIRE |
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