Dendritic cells derived from metastatic cancer patients vaccinated with allogeneic dendritic cell-autologous tumor cell hybrids express more CD86 and induce higher levels of interferon-gamma in mixed lymphocyte reactions.
Dendritic cells (DCs) are highly effective antigen-presenting cells that, when derived from cancer patients, seem to be functionally deficient. Herein, we show that vaccination with allogeneic DC-autologous tumor cell hybrids affects the phenotype and improves the function of monocyte-derived DCs (Mo-DCs) from cancer patients. Mononuclear cells were isolated from patients' peripheral blood by density gradient centrifugation, and adherent cells were cultured in medium containing GM-CSF plus IL-4 and, after 5 days, TNF-alpha. After 2 more days, Mo-DCs were harvested and their CD80, CD86, and CD83 expression was assessed by flow cytometry. They were also used as stimulators in mixed lymphocyte reactions (MLR), where IFN-gamma production was measured by ELISA. Mo-DCs from unvaccinated patients expressed significantly lower levels of CD86, and tended to express lower levels of CD83 than Mo-DCs from healthy donors. However, Mo-DCs generated after hybrid cell vaccination presented increased expression of the same markers and induced significantly higher levels of IFN-gamma in MLR. These results indicate that the use of allogeneic DC-based cancer vaccines induces recovery of DC function in metastatic cancer patients and, therefore, could precede the use of autologous DCs for vaccine preparation. Such an approach could be relevant and should be investigated in clinical trials.
Neves
Andreia R
AR
Departamento de Imunologia, ICB-USP, Av. Prof. Lineu Prestes, 1730, São Paulo, SP, 05508-000, Brazil.
Ensina
Luis Felipe C
LF
Anselmo
Luciene B
LB
Leite
Katia R M
KR
Buzaid
Antonio C
AC
Câmara-Lopes
Luiz H
LH
Barbuto
José Alexandre M
JA
D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D005786:Gene Expression Regulation; D006801:Humans; D006822:Hybrid Cells / Q000276:immunology / Q000637:transplantation*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D008545:Melanoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D009362:Neoplasm Metastasis; D010641:Phenotype
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D019496:Cancer Vaccines; D008562:Membrane Glycoproteins; D007371:Interferon-gamma