期刊
HAEMATOLOGICA
卷 98, 期 3, 页码 376-384出版社
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.2012.072835
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类别
资金
- Leukaemia & Blood Foundation
- Genesis Oncology Trust [GOT-0702-RPG]
- NZ Lottery Grants Board [251788]
- Genzyme New Investigators Scholarship through the Haematology Society of Australia and New Zealand
Invariant natural killer T cells recognize glycolipid antigens such as alpha-galactosylceramide presented by CD1d. In preclinical models of B-cell malignancies, alpha-galactosylceramide is an adjuvant to tumor vaccination, enhancing tumor-specific T-cell responses and prolonging survival. However, numerical and functional invariant natural killer T-cell defects exist in patients with some cancers. Our aim was to assess this axis in patients with chronic lymphocytic leukemia. The numbers of circulating invariant natural killer T cells and the expression of CD1d on antigen-presenting cells were evaluated in patients with chronic lymphocytic leukemia and age-matched controls. Cytokine profile and in vitro proliferative capacity were determined. Patient- and control-derived invariant natural killer T-cell lines were generated and characterized, and allogeneic and autologous responses to alpha-galactosylceramide-treated leukemia cells were assessed. Absolute numbers and phenotype of invariant natural killer T cells were nounal in patients with untreated chronic lymphocytic leukemia, and cytokine profile and proliferative capacity were intact. Chemotherapy-treated patients had reduced numbers of invariant natural killer T cells and myeloid dendritic cells, but alpha-galactosylceramide-induced proliferation was preserved. Invariant natural killer T-cell lines from patients lysed CD id-expressing targets. Irradiated alpha-galactosylceramide-treated leukemic cells elicited allogeneic and autologous invariant natural killer T-cell proliferation, and alpha-galactosylceramide treatment led to increased proliferation of conventional T cells in response to tumor. In conclusion, the invariant natural killer T-cell and CD1d axis is fundamentally intact in patients with early-stage chronic lymphocytic leukemia and, despite reduced circulating numbers, function is retained in fludarabine-treated patients. Immunotherapies exploiting the adjuvant effect of alpha-galactosylceramide may be feasible.
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