The American journal of pathology, 2011-07, Vol.179 (1), p.436-451
2011
Details
- Autor(en) / Beteiligte
- Titel
- Human Renal Cell Carcinoma Induces a Dendritic Cell Subset That Uses T-Cell Crosstalk for Tumor-Permissive Milieu Alterations
- Ist Teil von
- The American journal of pathology, 2011-07, Vol.179 (1), p.436-451
- Ort / Verlag
- Bethesda, MD: Elsevier Inc
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Tissue dendritic cells (DCs) may influence the progression of renal cell carcinoma (RCC) by regulating the functional capacity of antitumor effector cells. DCs and their interaction with T cells were analyzed in human RCC and control kidney tissues. The frequency of CD209+ DCs in RCCs was found to be associated with an unfavorable TH 1 cell balance in the tissue and advanced tumor stages. The CD209+ DCs in RCC were unusual because most of them co-expressed macrophage markers (CD14, CD163). The phenotype of these enriched-in-renal-carcinoma DCs (ercDCs) could be reiterated in vitro by carcinoma-secreted factors (CXCL8/IL-8, IL-6, and vascular endothelial growth factor). ErcDCs resembled conventional DCs in costimulatory molecule expression and antigen cross-presentation. They did not suppress cognate cytotoxic T-lymphocyte function and did not cause CD3ζ down-regulation, FOXP3 induction, or T-cell apoptosis in situ or in vitro ; thus, they are different from classic myeloid-derived suppressor cells. ErcDCs secreted high levels of metalloproteinase 9 and used T-cell crosstalk to increase tumor-promoting tumor necrosis factor α and reduce chemokines relevant for TH 1-polarized lymphocyte recruitment. This modulation of the tumor environment exerted by ercDCs suggests an immunologic mechanism by which tumor control can fail without involving cytotoxic T-lymphocyte inhibition. Pharmacologic targeting of the deviated DC differentiation could improve the efficacy of immunotherapy against RCC.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0002-9440eISSN: 1525-2191DOI: 10.1016/j.ajpath.2011.03.011Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3123875
- Format
- –
- Schlagworte
- Adult, Aged, Aged, 80 and over, Apoptosis, Biological and medical sciences, Blotting, Western, Carcinoma, Renal Cell - immunology, Carcinoma, Renal Cell - metabolism, Carcinoma, Renal Cell - pathology, Case-Control Studies, Cell Differentiation, Cell Movement, Cell Proliferation, Chemokines - metabolism, Cross-Priming, Cytokines - metabolism, Dendritic Cells - immunology, Dendritic Cells - metabolism, Dendritic Cells - pathology, Endocytosis, Female, Flow Cytometry, Fluorescent Antibody Technique, Humans, Immunoenzyme Techniques, Interleukin-6 - metabolism, Investigative techniques, diagnostic techniques (general aspects), Kidney Neoplasms - immunology, Kidney Neoplasms - metabolism, Kidney Neoplasms - pathology, Kidneys, Male, Medical sciences, Middle Aged, Nephrology. Urinary tract diseases, Pathology, Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques, Phagocytosis, Regular, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger - genetics, T-Lymphocytes - immunology, T-Lymphocytes - metabolism, T-Lymphocytes - pathology, T-Lymphocytes, Cytotoxic - immunology, T-Lymphocytes, Cytotoxic - metabolism, T-Lymphocytes, Cytotoxic - pathology, Th1 Cells - immunology, Th1 Cells - metabolism, Th1 Cells - pathology, Tumor Cells, Cultured, Tumors of the urinary system