Human renal cell carcinoma induces a dendritic cell subset that uses T-cell crosstalk for tumor-permissive milieu alterations

Am J Pathol. 2011 Jul;179(1):436-51. doi: 10.1016/j.ajpath.2011.03.011. Epub 2011 May 18.


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 T(H)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 T(H)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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • 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
  • Kidney Neoplasms / immunology*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Phagocytosis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • 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


  • Chemokines
  • Cytokines
  • Interleukin-6
  • RNA, Messenger