CD40 stimulation induces differentiation of acute lymphoblastic leukemia cells into dendritic cells.
Despite the very high percentage of long-term remissions in acute lymphoblastic leukemia (ALL) in children, some of them suffer from recurrence of the disease. New treatment modalities, e.g. effective geno- and immunotherapy are needed. The use of neoplasmatic cells to present tumor antigens is one of the approaches in cancer vaccines. ALL cells lack the expression of costimulatory molecules and are poor antigen presenting cells (APCs) for T-cell activation. CD40/40L interaction stimulates B-cells to proliferate, differentiate, upregulate costimulatory molecules and increase antigen presentation. The aim of the study was to test the hypothesis that ALL cells can be turned into professional APCs by CD40L activation. Children with B-cell precursor ALL were enrolled into the study. Mononuclear cells from bone marrow or peripheral blood were stimulated with CD40L and interleukin 4.


RESULTS
1) after culture we noted upregulation of all assessed costimulatory, adhesion and activatory molecules i.e. CD1a, CD11c, CD40, CD54, CD80, CD83, CD86, CD123, HLA class I and II; 2) CD40L activated ALL cells induced proliferation of allogeneic T-cells (measured by [(3)H]thymidine incorporation). These results confirm the possibility of enhancing the immunogenicity of ALL cells with the CD40L system and indicate that this approach can be used in immunotherapeutic trials.
Luczyński
Włodzimierz
W
Department of Pediatric Oncology, Medical University of Białystok, Poland. w.luczynski@wp.pl
Stasiak-Barmuta
Anna
A
Iłendo
Elzbieta
E
Krawczuk-Rybak
Maryna
M
Malinowska
Iwona
I
Mitura-Lesiuk
Małgorzata
M
Parfieńczyk
Adam
A
Szymański
Marcin
M
D000938:Antigen-Presenting Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018949:Antigens, CD1 / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018122:B7-1 Antigen / Q000032:analysis; D039521:CD11c Antigen / Q000032:analysis; D019013:CD40 Antigens / Q000032:analysis*; D023201:CD40 Ligand / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007223:Infant; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000473:pathology
D018949:Antigens, CD1; D018122:B7-1 Antigen; D039521:CD11c Antigen; C419393:CD1a antigen; D019013:CD40 Antigens; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand; D015847:Interleukin-4