Cyclophosphamide-induced myeloid-derived suppressor cell population is immunosuppressive but not identical to myeloid-derived suppressor cells induced by growing TC-1 tumors

0381574 - ÚMG 2013 RIV US eng J - Journal Article
Mikyšková, Romana - Indrová, Marie - Polláková, Veronika - Bieblová, Jana - Šímová, Jana - Reiniš, Milan
Cyclophosphamide-induced myeloid-derived suppressor cell population is immunosuppressive but not identical to myeloid-derived suppressor cells induced by growing TC-1 tumors.
Journal of Immunotherapy. Roč. 35, č. 5 (2012), s. 374-384. ISSN 1524-9557. E-ISSN 1537-4513
R&D Projects: GA ČR(CZ) GPP301/11/P220; GA ČR GA301/09/1024; GA ČR GA301/07/1410
EU Projects: European Commission(XE) 18933 - CLINIGENE
Institutional research plan: CEZ:AV0Z50520514
Institutional support: RVO:68378050
Keywords : myeloid-derived suppressor cells * cyclophosphamide * all-trans-retinoic acid * IL-12 * HPV16
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.463, year: 2012

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.
Permanent Link: http://hdl.handle.net/11104/0216407