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Cancer Immunology, Immunotherapy

, Volume 64, Issue 2, pp 161–171 | Cite as

Monocyte-derived dendritic cells reflect the immune functional status of a chromophobe renal cell carcinoma patient: Could it be a general phenomenon?

  • Maria A. Clavijo-Salomon
  • Rodrigo N. Ramos
  • Alexandre Crippa
  • Celia R. Pizzo
  • Patricia C. Bergami-Santos
  • Jose Alexandre M. BarbutoEmail author
Original Article

Abstract

Purpose

The chromophobe renal cell carcinoma (ChRCC), though associated with a hereditary cancer syndrome, has a good prognosis after tumor removal. The lack of recurrence could be related to the absence of immune system compromise in patients or to an effective functional recovery of immune functions after tumor removal. Thus, we evaluated monocyte-derived dendritic cells (Mo-DCs) in a 34-year-old male who had a ChRCC, before and after tumor removal.

Methods

CD14+ monocytes from the patient’s peripheral blood, 1 week before and 3 months after partial nephrectomy, were differentiated in vitro into immature and mature Mo-DCs. These were harvested, analyzed by flow cytometry and used as stimulators of allogeneic T cells. Supernatants from cultures were collected for cytokine analysis.

Results

Tumor removal was associated with decreased expression of PD-L1, but also, surprisingly, of CD205, HLA-DR, CD80 and CD86 by Mo-DCs. Also, Mo-DC’s ability to stimulate T cell proliferation increased, along with IL-2Rα expression and IFN-γ production. Simultaneously, the patients’ Mo-DCs ability to induce Foxp3+ T cells decreased after surgery. One-year postoperative follow-up shows no tumor recurrence.

Conclusion

The presence of a ChRCC affected Mo-DCs generated in vitro, which recovered their function after tumor removal. This indicates that the favorable outcome observed after ChRCC resection may be due to the restoration of immunocompetence. Furthermore, since functional alterations described for DCs within tumors may be also found in Mo-DCs, their accurate functional analysis—not restricted to the determination of their surface immunophenotype—may provide an indirect “window” to the tumor microenvironment.

Keywords

Monocyte-derived dendritic cells T cell anergy Foxp3+ T cells Chromophobe renal cell carcinoma 

Abbreviations

CFSE

Carboxyfluorescein succinimidyl ester

ChRCC

Chromophobe renal cell carcinoma

CT scan

Computed axial tomography

Foxp3

Forkhead box P3

FSC

Forward scatter

GM-CSF

Granulocyte macrophage colony-stimulating factor

IFN-γ

Interferon gamma

DCs

Dendritic cells

IL-2Rα

Alpha chain of interleukin 2 receptor (CD25)

IL-4

Interleukin 4

MFI

Media fluorescence intensity

Mo-DCs

Monocyte-derived dendritic cells

Mo-iDCs

Monocyte-derived immature dendritic cells

Mo-mDCs

Monocyte-derived mature dendritic cells

MRI

Magnetic resonance imaging

NS Ctrl

Non-stimulated control T cells

PBMCs

Peripheral blood mononuclear cells

PD-L1

Programmed cell death ligand 1

PHA

Phytohaemagglutinin

SSC

Side scatter

TNF-α

Tumor necrosis factor alpha

Notes

Acknowledgments

This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP (2009/54599-5, 2011/05331-0 and 2012/23478-0) and Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq. We thank Instituto HOC—Hospital Alemão Oswaldo Cruz, São Paulo—Brazil and Dr. Adilson Kleber Ferreira for the critical reading of this manuscript. This work is dedicated to the patient.

Conflict of interest

The authors declare no financial or other conflict.

Ethical standard

Blood samples and images were collected after written informed consent signed by the patient and the healthy donors, who agreed with the publication of this case report.

Supplementary material

262_2014_1625_MOESM1_ESM.pdf (434 kb)
Supplementary material 1 (PDF 433 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Maria A. Clavijo-Salomon
    • 1
  • Rodrigo N. Ramos
    • 1
  • Alexandre Crippa
    • 2
  • Celia R. Pizzo
    • 1
  • Patricia C. Bergami-Santos
    • 1
  • Jose Alexandre M. Barbuto
    • 1
    • 3
    Email author
  1. 1.Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical SciencesUniversity of Sao PauloSão PauloBrazil
  2. 2.Section of Uro-Oncology of the São Paulo State Cancer Institute - ICESP, Division of UrologyUniversity of São Paulo Medical SchoolSão PauloBrazil
  3. 3.Cell and Molecular Therapy Center NUCEL-NETCEMUniversity of Sao PauloSao PauloBrazil

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