Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine
| Autor: | Veronica Huber, Chiara Castelli, Paola Canese, Manuela Iero, Paola Filipazzi, Licia Rivoltini, Roberta Valenti, Luigi Mariani, Lorenzo Pilla, Giorgio Parmiani |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Cancer Research Myeloid Enzyme-Linked Immunosorbent Assay Peripheral blood mononuclear cell Cancer Vaccines T-Lymphocytes Regulatory Flow cytometry Blood cell Medicine Humans Myeloid Cells Neoplasm Metastasis Melanoma Interferon alfa Heat-Shock Proteins Whole blood medicine.diagnostic_test business.industry Granulocyte-Macrophage Colony-Stimulating Factor HLA-DR Antigens medicine.disease Flow Cytometry medicine.anatomical_structure Granulocyte macrophage colony-stimulating factor Phenotype Treatment Outcome Oncology Immunology Female business medicine.drug |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 25(18) |
| ISSN: | 1527-7755 |
| Popis: | PurposePhenotypic and functional features of myeloid suppressor cells (MSC), which are known to serve as critical regulators of antitumor T-cell responses in tumor-bearing mice, are still poorly defined in human cancers. Here, we analyzed myeloid subsets with suppressive activity present in peripheral blood of metastatic melanoma patients and evaluated their modulation by a granulocyte-macrophage colony-stimulating factor (GM-CSF) –based antitumor vaccine.Patients and MethodsStage IV metastatic melanoma patients (n = 16) vaccinated with autologous tumor-derived heat shock protein peptide complex gp96 (HSPPC-96) and low-dose GM-CSF provided pre- and post-treatment whole blood specimens. Peripheral-blood mononuclear cells (PBMCs) were analyzed by flow cytometry, separated into cellular subsets, and used for in vitro proliferation assays. PBMCs from stage-matched metastatic melanoma patients (n = 12) treated with non–GM-CSF-based vaccines (ie, HSPPC-96 alone or interferon alfa/melanoma–derived peptides) or sex- and age-matched healthy donors (n = 16) were also analyzed for comparison.ResultsThe lack of or low HLA-DR expression was found to identify a CD14+cell subset highly suppressive of lymphocyte functions. CD14+HLA-DR–/locells were significantly expanded in all metastatic melanoma patients, whereas they were undetectable in healthy donors. Suppressive activity was mediated by transforming growth factor beta (TGF-β), whereas no involvement of the arginase and inducible nitric oxide synthase pathways could be detected. CD14+HLA-DR–/locells, as well as spontaneous ex vivo release and plasma levels of TGF-β, were augmented after administration of the HSPPC-96/GM-CSF vaccine. No enhancement of the CD14+-mediated suppressive activity was found in patients receiving non–GM-CSF-based vaccines.ConclusionCD14+HLA-DR–/locells exerting TGF-β–mediated immune suppression represent a new subset of MSC potentially expandable by the administration of GM-CSF–based vaccines in metastatic melanoma patients. |
| Databáze: | OpenAIRE |
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