Background Invariant natural killer T cells recognise glycolipid antigens such as α- galactosylceramide presented by CD1d. In preclinical models of B cell malignancies, α-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. We aimed to assess this axis in patients with chronic lymphocytic leukemia. Design and methods Circulating invariant natural killer T cell numbers and antigen presenting cell CD1d expression were measured 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 α-galactosylceramide-treated leukemia cells were assessed. Results Absolute numbers and phenotype of invariant natural killer T cells were normal in untreated chronic lymphocytic leukemia, and cytokine profile and proliferative capacity were intact. Chemotherapy-treated patients had reduced invariant natural killer T and myeloid dendritic cell numbers, but α- galactosylceramide-induced proliferation was preserved. Invariant natural killer T cell lines from patients lysed CD1d-expressing targets. Irradiated α-galactosylceramide- treated leukemic cells elicited allogeneic and autologous invariant natural killer T cell proliferation, and α-galactosylceramide treatment led to increased proliferation of conventional T cells in response to tumor. Conclusions 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 α-galactosylceramide may be feasible.
- Received June 26, 2012.
- Accepted September 12, 2012.
- Copyright © 2012, Ferrata Storti Foundation