Human renal cell carcinoma induces a dendritic cell subset that uses T-cell crosstalk for tumor-permissive milieu alterations
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Updated: May 31, 2026
Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells
Published on: August 1, 2025
Ainhoa-M Figel1, Dorothee Brech, Petra U Prinz
1Institute of Molecular Immunology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.
Abstract:
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.
Insights
Dendritic cells (DCs) in renal cell carcinoma (RCC) promote tumor growth by altering the immune microenvironment, not by directly suppressing T cells. Targeting DC differentiation may enhance RCC immunotherapy effectiveness.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Tissue dendritic cells (DCs) play a crucial role in regulating antitumor immune responses.
- The specific role of DCs in the progression of renal cell carcinoma (RCC) remains incompletely understood.
- Understanding DC function in RCC is vital for developing effective immunotherapies.
Purpose of the Study:
- To investigate the phenotype and function of dendritic cells (DCs) in human renal cell carcinoma (RCC) tissues.
- To determine the impact of RCC-associated DCs on T cell responses and the tumor microenvironment.
- To explore potential therapeutic strategies targeting DC differentiation in RCC.
Main Methods:
- Analysis of DC populations and their interaction with T cells in human RCC and control kidney tissues.
- Characterization of CD209(+) DCs in RCC, including co-expression of macrophage markers.
- In vitro studies to reiterate DC phenotype using carcinoma-secreted factors and assess T cell function.
- Measurement of secreted factors by DCs, including metalloproteinase 9 and cytokines.
Main Results:
- CD209(+) DCs in RCC were associated with an unfavorable T(H)1 balance and advanced tumor stages.
- These DCs (ercDCs) co-expressed macrophage markers and could be induced by carcinoma-secreted factors.
- ErcDCs did not suppress cytotoxic T-lymphocyte function but secreted metalloproteinase 9 and modulated cytokine profiles to promote tumor growth.
- ErcDCs altered the tumor microenvironment by increasing tumor necrosis factor α and reducing T(H)1-recruiting chemokines.
Conclusions:
- RCC-associated dendritic cells (ercDCs) exhibit a unique phenotype and promote tumor progression through microenvironment modulation rather than direct T cell suppression.
- These findings reveal a novel immunologic mechanism of tumor immune evasion in RCC.
- Targeting the aberrant differentiation of DCs presents a promising strategy to enhance the efficacy of immunotherapy for renal cell carcinoma.
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