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 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.
Authors' Affiliations: Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center, Heidelberg, Germany.
Yago
Y
Pico de Coaña
Isabel
I
Poschke
Giusy
G
Gentilcore
Yumeng
Y
Mao
Maria
M
Nyström
Johan
J
Hansson
Giuseppe V
GV
Masucci
Rolf
R
Kiessling
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017951:Antigen Presentation / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001119:Arginase / Q000378:metabolism*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D006098:Granulocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; D000074324:Ipilimumab; C574619:ARG1 protein, human; D001119:Arginase