Leukemia derived dendritic cells (LDCs) may be ineffective as a cancer vaccine for acute myeloid leukemia (AML)

Abstract

2527 Background: Dendritic cells generated from leukemic blasts (LDCs) are being explored as a strategy for generating anti-leukemia immunity. Optimizing this approach requires understanding the phenotypic and functional characteristics of LDCs. Methods: Leukemia blasts were isolated from peripheral blood of patients with AML. CD34 selection was performed on a subset of specimens. DCs were generated by culturing blasts in the presence of GM-CSF, IL-4 and TNFa for 7 days. LDC phenotype was analysed by flow cytometry, and was compared to fusions of leukemic blasts and allogeneic DCs derived from healthy donors. The capacity of LDCs to stimulate T cell proliferation and TH1 polarization was examined. Results: Compared to undifferentiated blasts, LDCs increased expression of HLA-DR and CD 11C (mean expression 77% and 62%). In contrast, LDCs did not strongly express costimulatory molecules CD80 or CD86 (mean expression 9% and 18%) or the maturation marker CD83 (mean expression 4%). In the subset of blasts that underwent CD34 selection, DC differentiation did not induce expression of CD 80, CD83, or CD86 (mean expression 6%, 2%, 9%). Culture of CD34- population with GM-CSF, IL-4 and TNFa resulted in moderate expression of CD 80, CD83 and CD86 (22%, 19.8% and 50.6% respectively). Of note, expression of tumor antigen CD117 (c-Kit) decreased after cytokine differentiation (mean expression 54% at baseline to 24% on LDCs). In contrast, fusion cells expressed both CD117 and CD86 (mean fusion efficiency 28%). Allogeneic T cell proliferation in response to stimulation by leukemic DC (mean SI 13.2, ratio 30:1) was higher than after stimulation with undifferentiated blasts (mean SI 6.8, ratio 30:1). However, neither stimulation with blasts nor with leukemic DC induced T cell expression of interferonγ. Conclusions: LDCs do not express costimulatory molecules and lose expression of tumor antigens, while fusion cells express both. LDCs stimulate allogeneic T cell proliferation but induce T cell expression of interferon gamma poorly. These results suggest that LDCs may be tolerogenic. Strategies to enhance the ability of LDCs to stimulate anti-tumor immunity are being explored, as are the functional properties of fusion cells. No significant financial relationships to disclose.