Ipilimumab treatment results in an early decrease in the frequency of circulating granulocytic myeloid-derived suppressor cells as well as their Arginase1 production

• Published in: Cancer immunology research 2013-09, Vol.1 (3), p.158-162
• Main Authors: Pico de Coaña, Yago, Poschke, Isabel, Gentilcore, Giusy, Mao, Yumeng, Nyström, Maria, Hansson, Johan, Masucci, Giuseppe V, Kiessling, Rolf
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - therapeutic use; Antigen Presentation - immunology; Antineoplastic Agents - therapeutic use; Arginase - metabolism; CTLA-4 Antigen - antagonists & inhibitors; Granulocytes - drug effects; Granulocytes - enzymology; Granulocytes - immunology; Humans; Ipilimumab; Male; Melanoma - drug therapy; Melanoma - immunology; Middle Aged; Skin Neoplasms - drug therapy; Skin Neoplasms - immunology; T-Lymphocytes, Regulatory - immunology
• ISSN: 2326-6066; 2326-6074
• DOI: 10.1158/2326-6066.CIR-13-0016

Blocking the immune checkpoint molecule CTL antigen-4 (CTLA-4) with ipilimumab has proven to induce long-lasting clinical responses in patients with metastatic melanoma. To study the early response that takes place after CTLA-4 blockade, peripheral blood immune monitoring was conducted in five patients undergoing ipilimumab treatment at baseline, three and nine weeks after administration of the first dose. Along with T-cell population analysis, this work was primarily focused on an in-depth study of the myeloid-derived suppressor cell (MDSC) populations. Ipilimumab treatment resulted in lower frequencies of regulatory T cells along with reduced expression levels of PD-1 at the nine-week time point. Three weeks after the initial ipilimumab dose, the frequency of granulocytic MDSCs was significantly reduced and was followed by a reduction in the frequency of arginase1-producing CD3(-) cells, indicating an indirect in trans effect that should be taken into account for future evaluations of ipilimumab mechanisms of action.