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Cyclophosphamide-mediated immunomodulatory effects: an action on dendritic cells (DC)?

C M Cavalcanti F Maluf; A C Buzaid; S C Martins; José Alexandre Marzagão Barbuto; Meeting of the Brazilian Society for Immunology (31. 2006 Búzios)

Abstracts São Paulo, SP: Brazilian Society for Immunology, 2006

São Paulo 2006

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  • Título:
    Cyclophosphamide-mediated immunomodulatory effects: an action on dendritic cells (DC)?
  • Autor: C M Cavalcanti
  • F Maluf; A C Buzaid; S C Martins; José Alexandre Marzagão Barbuto; Meeting of the Brazilian Society for Immunology (31. 2006 Búzios)
  • Assuntos: IMUNOLOGIA
  • É parte de: Abstracts São Paulo, SP: Brazilian Society for Immunology, 2006
  • Notas: Disponível em CD-ROM
  • Descrição: Introduction & Objectives: Cyclophosphamide (Cy) has been used as an immunomodulatory drug, capable of enhancing immune responses in vaccination protocols. However, its mechanisms of action remain unclear. One possibility would be that the Cy-induced hematopoietic response generates a more favourable environment for the differentiation of effective DC. To test this hypothesis we studied the in vitro differentiation of DC from blood monocytes obtained from cancer patients treated with Cy, in two vaccination protocols for advanced/metastatic cancer. Methods & Results: Patients that received 300 mg/m2 of Cy iv, three days before vaccination against their tumour donated peripheral blood mononuclear cells (PBMC) before Cy administration and three days thereafter. PBMC were separated by density gradient centrifugation and cultured for 7 days with IL-4 and GM-CSF. At day 5, TNF-a was added to the culture. At the end of the culture period, the expression of the CD1a, CD11c, HLADR, CD86, CD80, CD83, CCR7 and CD14 was evaluated by flow cytometry. The frequency of CD86+ cells in the cultures was significantly higher after Cy treatment (14.2% x 23.1%; p=0.002). Furthermore, non-vaccinated patients showed a significantly higher increase in CD86+ cell frequency than those previously vaccinated (p= 0.05). In one sample tested, cells differentiated from monocytes obtained after Cy treatment induced stronger allogeneic T lymphocyte proliferation than cells
    derived from monocytes collected before treatment of the same patient (proliferation indexes of 2.53 x 1.39). Conclusions: These data support the hypothesis that Cy treatment affects PBMC ability to differentiate in response to DC differentiation stimuli. Such effect could contribute to the immune enhancing activity of this drug and should be considered in the design of future studies.
  • Editor: São Paulo
  • Data de criação/publicação: 2006
  • Formato: res. CL.025.
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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