Acute lymphoblastic leukemia-derived dendritic cells express tumor associated antigens: PNPT1, PMPCB, RHAMM, BSG and ERCC1.
In all types of leukemia both in children and adults there is a need for novel therapies that could reduce the risk of relapse after standard treatment. Acute lymphoblastic leukemia (ALL) cells are ineffective antigen presenting cells, but as shown by many authors including results from our laboratory, stimulation with CD40L restores their antigen expressing capacity. The development of T-cell therapies for leukemic patients can be based on discovery of leukemia-associated antigens (LAA) which could be recognized by the host immune system. The aim of our present study was to test the hypothesis that leukemia-derived dendritic cells maintain the expression of tumor associated antigens. Twenty five children with B-cell precursor ALL were prospectively enrolled into the study. The mononuclear cells from peripheral blood or bone marrow were cultured and stimulated (or not) with CD40L and IL-4. The assessment of costimulatory/adhesion molecules with the use of flow cytometry and real-time RT PCR were used to confirm the possibility of turning ALL cells into dendritic-like cells. Additionally 22 tumor associated antigens mRNA levels were determined by real-time PCR technique with the TaqMan chemistry using ready-to-use Low Density Arrays for Gene Expression. The results of the study showed maintained expression and even up-regulation of some (PNPT1, PMPCB, HMMR/RHAMM, BSG and ERCC1) tumor associated antigens in CD40-activated leukemic cells. CD40L stimulation leading to the differentiation of leukemic cells into DCs which combine both antigen presenting function and expression of tumor associated antigens represents an interesting approach in cancer immunotherapy.
Luczynski
W
W
Department of Pediatric Oncology and Hematology, Medical University of Bialystok, Bialystok, Poland. w.luczynski@wp.pl
Kowalczuk
O
O
Stasiak-Barmuta
A
A
Ilendo
E
E
Krawczuk-Rybak
M
M
Chyczewski
L
L
D000951:Antigens, Neoplasm / Q000235:genetics*; D051926:Basigin / Q000235:genetics*; D023201:CD40 Ligand / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D003713:Dendritic Cells / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics*; D005095:Exoribonucleases / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D007167:Immunotherapy; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000628:therapy; D012333:RNA, Messenger / Q000032:analysis; D000096122:Mitochondrial Processing Peptidase; D024101:Mitochondrial Proteins
D000951:Antigens, Neoplasm; D051926:Basigin; D023201:CD40 Ligand; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005095:Exoribonucleases; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D015847:Interleukin-4; D008666:Metalloendopeptidases; D012333:RNA, Messenger; D000096122:Mitochondrial Processing Peptidase; C497886:BSG protein, human; C098946:hyaluronan-mediated motility receptor; C071447:ERCC1 protein, human; C476417:PNPT1 protein, human; D024101:Mitochondrial Proteins