Cytokine upregulation of the antigen presenting function of acute myeloid leukemia cells

Acute myeloid leukemia (AML) cells are malignant counterparts of normal mye loid pathway progenitors. Myeloid progenitors differentiate into profession al antigen presenting cells (APC) under the essential influence of GM-CSF a long with additional cytokines. Twelve cases of human AML were tested for a bility to be differentiated toward a professional APC phenotype in short-te rm culture with addition of GM-CSF and the following recombinant proteins: TNF alpha, IL-4, CD40 ligand, Flt3 ligand and SCF. Significant upregulation of CD80 (B7-1) and enhancement of alloantigen presentation was seen with t he addition of GMCSF and TNF alpha alone or with additional cytokines. The combination of GM-CSF and TNF alpha, either alone or in combination with an additional cytokine, resulted in enhancing alloantigen presentation by at least two-fold over the media control group in 10/12 patients studied, and resulted in CD80 expression of greater than 15% in 11/12 patients studied. In AML cultures with GM-CSF and TNF alpha, coexpression of CD80 and either CD34 or an aberrant surface marker (CD56) was seen. In one case, sorted CD8 0(+) cells retained a characteristic cytogenetic marker and CD34 expression , proving their derivation from an AML precursor. These studies verify othe r reports of in vitro differentiation of human AML precursors into enhanced APC, suggesting that this phenomenon could be utilized for immunotherapy s trategies aimed at enhancing presentation of leukemia antigens to T cells.