Cancer Immunology Miniatures Ipilimumab Treatment Results in an Early Decrease in the Frequency of Circulating Granulocytic Myeloid-Derived Suppressor Cells as well as Their Arginase1 Production

Blocking the immune checkpoint molecule CTL antigen-4 (CTLA-4) with ipilimumab has proven to induce long-lasting clinical responses in patients withmetastaticmelanoma. 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 Tcell 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.