Expression and induction of costimulatory and adhesion molecules on acute myeloid leukemic cells: Implications for adoptive immunotherapy

Objective. Previously, we observed an increased recognition of malignant ce lls by cytotoxic T lymphocytes (CTL) when the target cells were cultured in vitro for 24 hours. In this study, we analyzed the expression of costimula tory and adhesion molecules on acute myeloid leukemia (AML) cells and deter mined whether 24-hour culture of the cells was associated with upregulation of these molecules. We analyzed whether this incubation period improved re cognition of AML cells by CTL. Materials and Methods. Expression of costimulatory and adhesion molecules o n Leukemic blasts of 34 patients comprising each AML FAB subclassification were analyzed directly and after 24 hours of culture, and the recognition o f these AML cells by an HLA-A2 restricted CTL clone was determined. Blockin g studies were performed with antibodies against CD54, CD58, and CD11a. Results, Immunophenotyping showed a low expression of CD80 and CD40 and a v ariable CD86 expression on most AML cells. CD54 expression was generally lo w, CD58 expression was high, and CD11a expression was variable, with a high er expression in AML MO, M1, M4, and M5. Twenty-four hours of culture resul ted in a significant upregulation of CD40, CD54, and CD58, Impaired recogni tion of AML cells by the HLA-AZ restricted CTL clone was enhanced 100-200 % by 24 hours of preincubation of the leukemic cells. Blocking studies showe d the importance of multiple adhesion molecules on the AML cells. Conclusion. Low expression of multiple costimulatory and adhesion molecules on AML could be upregulated by 24 hours of culture, which was associated w ith increased recognition of the AML blasts by CTL, Blocking multiple adhes ion molecules completely abolished CTL recognition, showing the importance of the combination of these molecules for T-cell interaction with AML, (C) 2000 International Society for Experimental Hematology. Published by Elsevi er Science Inc.