<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "The Role of CCR5 in the Recruitment of MDSC\r\nto the Tumor Microenvironment"^^ . "The aim of the study was to analyze the recruitment and accumulation of MDSC in the tumor\r\nmicroenvironment via C-C chemokine receptor type 5 (CCR5)/CRR5 ligand interaction, as well\r\nas immunosuppressive activity of CCR5-expressing tumor-infiltrating MDSC. We\r\ndemonstrated that CCR5+ Mo-MDSC and CCR5+ Gr-MDSC accumulated during tumor\r\nprogression in melanoma lesions of ret transgenic mice, as well as in melanoma patients at\r\ndifferent stages. In the mouse model, the frequency of CCR5+ cells was higher among\r\nGr-MDSC than among Mo-MDSC, whereas in melanoma patients, Mo-MDSC were\r\ncharacterized by higher frequency of CCR5+ cells. CCR5+ MDSC demonstrated an increased\r\nimmunosuppressive phenotype reflected by enhanced NO and ROS production, as well as\r\nARG-1 and PD-L1 expression, as compared to their CCR5- counterpart. Both in mouse model\r\nand in melanoma patients, the concentration of CCR5 ligands such as CCL3 (MIP-1α), CCL4\r\n(MIP-1β) and CCL5 (RANTES) and inflammatory factors such as granulocyte/macrophage\r\ncolony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), interleukin\r\n(IL)-6 and interferon-γ (IFN-γ) were increased in skin tumors as compared to the serum that\r\nallows the migration of these cells to the tumor microenvironment. Furthermore, we\r\ndemonstrated that CCR5+ MDSC inhibited T cell proliferation in a dose-dependent manner and\r\nshowed a tendency to stronger inhibition of T cell proliferation than their CCR5- counterparts.\r\nIn addition, we detected the CCR5 expression on CD4+ and CD8+ T cells in ret transgenic\r\nmelanoma bearing mice. Interestingly, the frequency of CCR5+ regulatory T cells (Treg) was\r\nsignificantly higher than that among other T cell subsets. Antigen-experienced CCR5+ Treg\r\naccumulated in advanced stage melanoma patients as compared to early stage patients and\r\nhealthy donor (HD). After intraperitoneal injection of mCCR5-Ig, which blocks CCR5-CCR5\r\nligand interactions into tumor bearing mice, we observed a significantly increase in mouse\r\nsurvival as compared to the control group. Moreover, the frequency of MDSC and Treg\r\ndecreased in skin tumors after mCCR5-Ig therapy. NO production by MDSC in skin tumors\r\nand the frequency of CD69 expression, reduced activated Treg in metastatic lymph nodes\r\n(LN), which indicates the therapeutic effect of mCCR5-Ig.\r\nIn summary, we demonstrated that during melanoma progression, CCR5 expressing MDSC\r\naccumulated in the tumor microenvironment and exerted strong immunosuppressive activity.\r\nThis accumulation was mediated by CCR5 ligands and other inflammatory factors. Blockage\r\nof CCR5-CCR5 ligand interactions induced the prolongation of the survival of tumor bearing\r\nmice mediated by a reduced migration and immunosuppressive activity of MDSC and Treg at\r\nthe tumor site. Our findings define a critical role for CCR5 in recruiting MDSC and Treg,which can be used for the development of novel immunotherapeutic strategies for\r\nmelanoma patients."^^ . "2016" . . . . . . . "Carolin"^^ . "Blattner"^^ . "Carolin Blattner"^^ . . . . . . "The Role of CCR5 in the Recruitment of MDSC\r\nto the Tumor Microenvironment (PDF)"^^ . . . "Dissertation_Carolin Blattner_final.pdf"^^ . . . "The Role of CCR5 in the Recruitment of MDSC\r\nto the Tumor Microenvironment (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "The Role of CCR5 in the Recruitment of MDSC\r\nto the Tumor Microenvironment (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "The Role of CCR5 in the Recruitment of MDSC\r\nto the Tumor Microenvironment (Other)"^^ . . . . . . "preview.jpg"^^ . . . "The Role of CCR5 in the Recruitment of MDSC\r\nto the Tumor Microenvironment (Other)"^^ . . . . . . "medium.jpg"^^ . . . "The Role of CCR5 in the Recruitment of MDSC\r\nto the Tumor Microenvironment (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #21870 \n\nThe Role of CCR5 in the Recruitment of MDSC \nto the Tumor Microenvironment\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .