Monocyte-derived dendritic cells reflect the immune functional status of a chromophobe renal cell carcinoma patient: Could it be a general phenomenon?
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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.
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.
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.
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.
KeywordsMonocyte-derived dendritic cells T cell anergy Foxp3+ T cells Chromophobe renal cell carcinoma
Carboxyfluorescein succinimidyl ester
Chromophobe renal cell carcinoma
- CT scan
Computed axial tomography
Forkhead box P3
Granulocyte macrophage colony-stimulating factor
Alpha chain of interleukin 2 receptor (CD25)
Media fluorescence intensity
Monocyte-derived dendritic cells
Monocyte-derived immature dendritic cells
Monocyte-derived mature dendritic cells
Magnetic resonance imaging
- NS Ctrl
Non-stimulated control T cells
Peripheral blood mononuclear cells
Programmed cell death ligand 1
Tumor necrosis factor alpha
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.
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.
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