B-cell chronic lymphocytic leukemia-derived dendritic cells stimulate allogeneic T-cell response and express chemokines involved in T-cell migration.
Despite discovery of new therapeutic agents, including nucleoside analogs and monoclonal antibodies, the B-cell chronic lymphocytic leukemia (B-CLL) remains incurable. In recent years, some effort has been made in developing T-cell specific immunity against neoplasmatic cells. Reconstitution of effective costimulation and immunological response of host T-cells against CLL cells could be a potential approach in immunotherapeutic trials. CD40/CD40L system is involved in the survival and proliferation of normal and neoplasmatic B-cells. Some preclinical studies have shown that CD40 stimulation can differentiate leukemic cells into dendritic cells (DCs) and result in host response. In this study, we sought to determine whether B-CLL cells could be turned into efficient and functional antigen presenting cells, as well as to assess the type of allogeneic T-cell response against B-CLL - derived DCs.


METHODS
B-CLL cells from 25 patients were cultured with or without the presence of CD40L and IL-4 for 96 hours and then cultured in mixed lymphocyte reaction with allogeneic T-cells.


RESULTS
1) after CD40 stimulation B-CLL cells achieved phenotypical and functional characterization of DCs (i.e. upregulated co-stimulatory and adhesion molecules at mRNA and protein level) 2) leukemia-derived DCs expressed higher amount of mRNA for chemokines involved in T-cell migration (MDC, TARC and CCR7) 3) the proliferating response of Tcells against leukemia-derived DCs consisted of CD4 and CD8 cells (upregulation of HLA-DR and OX40).


CONCLUSIONS
our experiment confirm that B-CLL cells can be turned into dendritic-like cells, additionally, these cells express chemokines involved in T-cell migration and stimulate allogeneic response.
Łuczyński
W
W
Department of Pediatric Oncology, Medical University of Białystok, Poland. w.luczynski@wp.pl
Stasiak-Barmuta
A
A
Piszcz
J
J
Iłendo
E
E
Kowalczuk
O
O
Krawczuk-Rybak
M
M
D000368:Aged; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D023201:CD40 Ligand / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000628:therapy; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D053262:Receptors, OX40 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous
D018925:Chemokines; D006684:HLA-DR Antigens; D053262:Receptors, OX40; D023201:CD40 Ligand