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

Author(s)

Clavijo-Salomon, Maria A. ^[1] ; Ramos, Rodrigo N. ^[1] ; Crippa, Alexandre ^[2] ; Pizzo, Celia R. ^[1] ; Bergami-Santos, Patricia C. ^[1] ; Barbuto, Jose Alexandre M. ^{[3, 1]}

Affiliation

^[1] Univ Sao Paulo, Lab Tumor Immunol, Dept Immunol, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Sao Paulo State Canc Inst ICESP, Sect Urooncol, Div Urol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Cell & Mol Therapy Ctr NUCEL NETCEM, Sao Paulo - Brazil

• Document type: Journal article
• Source: CANCER IMMUNOLOGY IMMUNOTHERAPY; v. 64, n. 2, p. 161-171, FEB 2015.
• Web of Science Citations: 4

Abstract

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-2R alpha expression and IFN-gamma 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. (AU)

• FAPESP's process: 11/05331-0 - Study of the effect of natural killer cells on the in vitro differentiation of monocytes into dendritic cells in cancer patients
• Grantee: Maria Alejandra Clavijo Salomón
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 09/54599-5 - Dendritic cells: integrative elements of the immune system - an applied approach
• Grantee: Jose Alexandre Marzagão Barbuto
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/23478-0 - Effect of Natural Killer cells on the in vitro differentiation of monocytes into dendritic cells in cancer patients: study of the mechanisms involved
• Grantee: Maria Alejandra Clavijo Salomón
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)