Journal
CANCER IMMUNOLOGY RESEARCH
Volume 1, Issue 3, Pages 158-162Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-13-0016
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Funding
- Swedish Cancer Society [120598]
- Stockholm Cancer Society [121103]
- Swedish Medical Research Council [K2011-66X-15387-07-3VR]
- Stockholm City Council [20110070]
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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. (C) 2013 AACR.
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