乳腺癌细胞抗原负载的自体树突状细胞体内诱导特异性T细胞应答

Objective To explore the potential of autologous dendritic cells (DCs) loaded with breast tumor cells antigen in inducing tumor-specific T cells response in vivo. Methods Fresh tumor samples from patients with breast cancer were collected and made into apoptotic heat shock tumor cells. Peripheral blood mononuclear cells (PBMCs) were isolated. DCs were induced from monocytes with granulocytemacrophage colony-stimulating factor (rhGM-CSF) and interleukin-4 (rhIL-4) combination for 5 days. DCs were co-cultured with autologous apoptotic heat shock tumor cells for 48 h. Twenty-four patients with breast cancers received four vaccinations of auto-DCs at 1 st, 2nd, 4th, and 6th week with cell number from 4×106 to 6×106. Results The vaccinations were well tolerated, and most patients experienced improved quality of life after DC immunization. Cytokine levels including IL-2, IL-12, TNF-α and IFN-γ in sera were obviously increased after DC vaccination [(68. 5±12. 4), (118. 2±31. 5), (78. 3±11.5) and (92. 6±14. 9) ng/L respectively] as compared with those before vaccinations [(33. 8±7. 2), (48. 5±10. 9), (18. 7±5. 3 ) and (20. 5±6. 3) ng/L respectively]. Both antigen specific delayed type hypersensitivity (DTH) reaction and the frequency of antigen specific IFN-gamma+CD8+T lymphocytes were examined after 4 times of DC vaccinations. The DTH tests were positive in 7 out of 10 patients. The frequency of IFN-γ+CD8+T cells was enhanced in 4 out of 10 patients. One out of 24 patients experienced a progressive disease, while the others showed no progress during a follow-up period of 34 months. Conclusion Autologous DCs loaded with heat-shocked apoptotic breast cancer cells antigen elicit specific anti-tumor T cell immune responses companying with high levels of Thl type cytokine secretion. DCs vaccination after surgery may be a novel and effective combination tool for tumor treatment.

Specific T-cell response induced in vivo by dendritic cells loaded with breast tumor cells antigen