Miniatures Ipilimumab Treatment Results in an Early Decrease in the Frequency of Circulating Granulocytic Myeloid-Derived Suppressor Cells as well as Their Arginase 1 Production

Pico de Coaña and colleagues analyzed peripheral blood from patients undergoing ipilimumab treatment at weeks 0, 3, and 9 and found a sequential decrease in the frequencies of granulocytic MDSC and arginase1-producing CD3-negative cells. At week 9, they found a lower number of Tregs and reduced PD-1 surface expression in CD3-positive cells. 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. Cancer Immunol Res; 1(3); 158–62. ©2013 AACR.