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Cyclophosphamide-induced myeloid-derived suppressor cell population is immunosuppressive but not identical to myeloid-derived suppressor cells induced by growing TC-1 tumors
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SYSNO ASEP 0381574 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Cyclophosphamide-induced myeloid-derived suppressor cell population is immunosuppressive but not identical to myeloid-derived suppressor cells induced by growing TC-1 tumors Author(s) Mikyšková, Romana (UMG-J) RID
Indrová, Marie (UMG-J) RID
Polláková, Veronika (UMG-J)
Bieblová, Jana (UMG-J)
Šímová, Jana (UMG-J) RID
Reiniš, Milan (UMG-J) RIDSource Title Journal of Immunotherapy - ISSN 1524-9557
Roč. 35, č. 5 (2012), s. 374-384Number of pages 11 s. Language eng - English Country US - United States Keywords myeloid-derived suppressor cells ; cyclophosphamide ; all-trans-retinoic acid ; IL-12 ; HPV16 Subject RIV EB - Genetics ; Molecular Biology R&D Projects GPP301/11/P220 GA ČR - Czech Science Foundation (CSF) GA301/09/1024 GA ČR - Czech Science Foundation (CSF) GA301/07/1410 GA ČR - Czech Science Foundation (CSF) Institutional support UMG-J - RVO:68378050 CEZ AV0Z50520514 - UMG-J (2005-2011) UT WOS 000304045500002 DOI 10.1097/CJI.0b013e318255585a Annotation Myeloid-derived suppressor cells (MDSC) play an important role in tumor escape from antitumor immunity. MDSC accumulate in the lymphoid organs and blood during tumor growth and their mobilization was also reported after cyclophosphamide (CY) administration. In this communication, spleen MDSC accumulating after CY therapy (CY-MDSC) were compared with those expanded in mice bearing human papilloma viruses 16-associated TC-1 carcinoma (TU-MDSC). Although both CY-MDSC and TU-MDSC accelerated growth of TC-1 tumors in vivo, their phenotype and immunosuppressive function differed. CY-MDSC consisted of higher percentage of monocyte-like subpopulation and this was accompanied by lower relative expression of immunosuppressive genes and lower suppression of T-cell proliferation. After interferon-gamma stimulation, the expression of immunosuppressive genes increased, but the suppressive ability of CY-MDSC did not reach that of TU-MDSC. The phenotype and function of MDSC obtained from mice bearing TC-1 tumors treated with CY was, in general, found to lie between CY-MDSC and TU-MDSC. After in vitro cultivation of MDSC in the presence of interleukin 12 (IL-12), the percentage of CD11b(+)/Gr-1(+) cells decreased and was accompanied by an increase in the percentage of CD86(+)/MHCII+ cells. The strongest modulatory effect was noticed in the group of CY-MDSC. The susceptibility of CY-MDSC to all-trans-retinoic acid (ATRA) was also evaluated. In vitro cultivation with ATRA resulted in MDSC differentiation, and ATRA inhibited MDSC accumulation induced by CY administration. Our findings identified differences between CY-MDSC and TU-MDSC and supported the rationale for utilization of ATRA or IL-12 to alter MDSC accumulation after CY chemotherapy with the aim to improve its antitumor effect. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2013
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