Core-binding factor-beta positive acute myeloid leukaemia cells induce T-cell responses.
The addition of specific cytokines is a mandatory prerequisite for the generation and subsequent function of leukaemia-derived dendritic cells (DC) believed to induce specific T-cell responses. In this study, we report the ability of blasts derived from cytogenetically classified acute myeloid leukaemia (AML) cells with the inversion of chromosome 16 to stimulate allogeneic and autologous T cells without additional cytokines. They displayed a measurable immunogenic effect. Sixteen of 17 established, stable AML cell lines, growing primary tumour cells from patients with a variety of chromosomal abnormalities, altered their surface marker expression pattern in proliferating culture. They lost the progenitor markers CD33, CD13 and CD34 while significantly increasing expression of the co-stimulatory molecules CD80 and CD86. Four cell lines derived from inv(16) positive blasts mounted allogeneic as well as autologous T cell activation with concomitant expression of CD25 and CD69. Moreover, oligoclonal expanded T cells were able to lyse inv(16) AML blasts in a specific major histocompatibility complex class I-restricted and CD80-dependent manner. AML blasts with karyotypes other than inv(16) activated T cells, but without inducing a significant proliferation. We conclude from this study that AML blasts derived from inv(16) positive patients may be preferential targets for AML immunotherapy strategies.
Banat
G-A
GA
Department of Hematology and Oncology, Medical Centre University of Giessen, Klinikstr. 36, Giessen, Germany. a.banat@innere.med.uni-giessen.de
Ihlow
Kerstin
K
Usluoglu
Nurguel
N
Hoppmann
Sabine
S
Hoeck
Marianne
M
Pralle
Hans
H
D000208:Acute Disease; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D003601:Cytotoxicity Tests, Immunologic; D004268:DNA-Binding Proteins / Q000276:immunology*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007951:Leukemia, Myeloid / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000276:immunology*
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors