Ipilimumab treatment results in an early decrease in the frequency of circulating granulocytic myeloid-derived...

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.