Ipilimumab treatment results in an early decrease in the frequency of circulating granulocytic myeloid-derived suppressor cells as well as their Arginase1 production.
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Pico de Coaña Y, Poschke I, Gentilcore G, Mao Y, Nyström M, Hansson J, Masucci GV, Kiessling R
Cancer Immunol Res 1 (3) 158-162 [2013-09-00; online 2013-08-02]
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.
PubMed 24777678
DOI 10.1158/2326-6066.CIR-13-0016
Crossref 10.1158/2326-6066.CIR-13-0016
pii: 2326-6066.CIR-13-0016