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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: CANCER IMMUNOLOGY IMMUNOTHERAPY; v. 64, n. 2, p. 161-171, FEB 2015.
• Citações Web of Science: 4

Resumo

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)

• Processo FAPESP: 11/05331-0 - Estudo do efeito das células Natural Killer sobre a diferenciação in vitro de monócitos em células dendríticas em pacientes com câncer
• Beneficiário: Maria Alejandra Clavijo Salomón
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 09/54599-5 - Células dendríticas: elementos integrados do sistema imune - enfoque aplicado
• Beneficiário: Jose Alexandre Marzagão Barbuto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/23478-0 - Efeito das células Natural Killer sobre a diferenciação in vitro de monócitos em células dendríticas em pacientes com câncer: estudo de mecanismos envolvidos
• Beneficiário: Maria Alejandra Clavijo Salomón
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto