白血病血样经粒细胞-巨噬细胞集落刺激因子联合前列腺素 E1 处理后，与耐受性树突状细胞频率降低及对自体原始细胞的细胞毒性增强相关

Background: Acute myeloid leukemia (AML) is characterized by reduced antileukemic effector cells and increased immunosuppressive cell populations. Leukemia-derived dendritic cells (DC leu ), generated from 18 leukemic whole blood (WB) ex vivo using 'Kit-M' (clinically approved: GM-CSF + PGE1), lead to improved cytotoxicity against autologous blasts after mixed lymphocyte culture (MLC) with patients' T-cells. Methods: We studied Kit-M-mediated effects on frequencies of tolerogenic, immunosuppressive DC (DC tol ) and correlated findings with ex vivo-achieved antileukemic effects (increased intracellular IFNγ production/degranulation, blast lysis) and patients' clinical characteristics.

Results: We show significantly decreased frequencies of DC tol (and increased frequencies of mature DC leu ) without induced blast proliferation in Kit-M treated vs. untreated WB samples. After T-cell-enriched MLC with Kit-M pretreated vs. not pretreated, WB frequencies of regulatory (CD152+ T-cells) were significantly decreased, while 'activated' (IFNγ+, degranulating) non-naive, proliferating, memory, CD154+) T-cells, as well as NK and CIK-cells were (significantly) increased.

We found a (significant) positive correlation of achieved improved blast lysis, frequencies of DC leu and 'activated' (IFNγ+/degranulating) T- or NK/CIK cells, and a (significant) negative correlation with frequencies of DC tol and regulatory (CD152+ T-cells). Kit-M treatment of leukemic WB increases DC leu and decreases DC tol , correlating with improved immune reactions/improved cytotoxicity against autologous blasts, and downregulated suppressive T-cells in samples before or after MLC.

Conclusions: These findings demonstrate the potential of Kit-M (using clinically approved drug compositions) to treat AML patients to potentially overcome the immunosuppressive tumor microenvironment, leading to improved antileukemic responses-thereby stabilizing remission of the disease in AML patients.