CD40 stimulation induces differentiation of acute lymphoblastic leukemia cells into dendritic cells

• Autorzy: Luczynski W. , Stasiak-Barmuta A. , Ilendo E. , Krawczuk-Rybak M. , Malinowska I. , Mitura-Lesiuk M. , Parfienczyk A. , Szymanski M.
• Języki publikacji: EN

Abstrakty

EN

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 [3H]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.

Słowa kluczowe

EN

human disease; T lymphocyte; dendritic cell; child; acute lymphoblastic leukemia; immunotherapy

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2006
• Tom: 53
• Numer: 2
• Opis fizyczny: p.377-382,fig.,ref.

Twórcy

autor

Luczynski W.

• Medical University of Bialystok, Bialystok, Poland

autor

Stasiak-Barmuta A.

autor

Ilendo E.

autor

Krawczuk-Rybak M.

autor

Malinowska I.

autor

Mitura-Lesiuk M.

autor

Parfienczyk A.

autor

Szymanski M.

Bibliografia

• Biagi E, Dotti G, et al. (2005) Molecular transfer of CD40 and OX40 ligands to leukemic human B cells induces expansion of autologous tumor-reactive cytotoxic T lymphocytes. Blood 105: 2436–2442.
• Cignetti A, Bryant E, Allione B, Vitale A, Foa R, Cheever MA (1999) CD34+ acute myeloid and lymphoid leukemic blasts can be induced to differentiate into dendritic cells. Blood 94: 2048–2055.
• D’Amico G, Bugarin MV, Bianchi G, Pirovano G, Bonamino M, Marin V, Allavena P, Biagi E, Biondi A (2004a) CD40 activation of BCP-ALL cells generates IL-10 pro ducing, IL-12 defective APCs that induce allogeneic Tcell anergy. Blood 104: 744–751.
• D’Amico G, Marin V, Biondi A, Bonamino MH (2004b) Potential use of CD40 ligand for immunotherapy of childhood B-cell precursor acute lymphoblastic leukaemia. Best Pract Res Clin Hematol 17: 465–477.
• Ghia P, Transidico P, et al. (2001) Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T-cells. Blood 98: 533–540.
• Gruber TA, Skelton DC, Kohn DB (2002) Requirement for NK cells in CD40 ligand-mediated rejection of Philadelphia chromosome-positive acute lymphoblastic leukemia cells. J Immunol 168: 73–80.
• Haining WN, Cardoso AA, et al. (2005) Failure to define window of time for autologous tumor vaccination in patients with newly diagnosed or relapsed acute lymphoblastic leukemia. Exp Hematol 33: 286–294.
• Hoogendoorn M, Wolbers JO, Smit WM, Schaafsma MR, Barge RMY, Willemze R, Falkenburg JHF (2004) Generation of B-cell chronic lymphocytic leukemia (BCLL)- reactive T-celll lines and clones from HLA class I-matched donors using modified B-CLL cells as stimulators: implications for adoptive immunotherapy. Leukemia 18: 1278–1287.
• Kebelmann-Betzing C, Korner G, Badiali L, Buchwald D, Moricke A, Korte A, Kochling J (2001) Characterization of cytokine, growth factor receptor, costimulatory and adhesion molecule expression patterns of bone marrow blasts in relapsed childhood B cell precursor ALL. Cytokine 13: 39–50.
• Lee AJ, Haworth C, Hutchinson RM, Patel R, Carter R, James RFL (2001) Enhancement of cALL immunogenecity by co-culture with a CD154 expressing 293 cell line. Clin Exp Immunol 124: 359–368.
• Lee J, Sait SN, Wetzler M (2004) Characterisation of dendritic- like cells derived from t(9;22) acute lymphoblastic leukemia blasts. Int Immunol 16: 1377–1389.
• Łuczyński W, Stasiak-Barmuta A, Krawczuk-Rybak M (2004a) Immunologic monitoring of maintenance therapy for acute lymphoblastic leukaemia in children — preliminary report. Pediatr Blood Cancer 42: 416–420.
• Łuczyński W, Stasiak-Barmuta A, Krawczuk-Rybak M, Szymański M, Malinowska I, Mitura-Lesiuk M (2004b) Monocytes in children with leukemias and lymphomas — down-regulation of HLA and costimulatory molecules. Acta Biochim Polon 51: 1067–1073.
• Mielcarek M, Sperling C, Schrappe M, Meyer M, Riehm H, Ludwig WD (1997) Expression of intercellular adhesion molecule (ICAM-1) in childhood acute lymphoblastic leukemia: correlation with clinical features and outcome. Br J Haematol 96: 301–307.
• Mohty M, Isnardon D, Charbonnier A, Lafage-Pochitaloff M, Merlin M, Sainty D, Olive D, Gaugler B (2002) Generation of potent Th1 responses from patients with lymphoid malignancies after differentiation of B lymphocytes into dendritic cells. Int Immunol 14: 741–750.
• Todisco E, Gaipa G, Biagi E, Bonamino M, Gramigna R, Introna M, Biondi A (2002) CD40 ligand-stimulated B cell precursor leukemic cells elicit interferon-gamma production by autologous bone marrow T-cells in childhood acute lymphoblastic leukemia. Leukemia 16: 2046–2054.
• Urbaniak-Kujda D, Wołowiec D, Tomaszewska-Toporowska B, Jaźwiec B, Frydecka I, Kapelko-Słowik K, Kuliczkowski K (2004) Wpływ krótkoterminowych hodowli blastów ostrych białaczek na ekspresję cząsteczek kostymulujących i na zdolność indukcji proliferacji autologicznych limfocytów T. Adv Clin Exp Med 13: 567–573.
• von Bergwelt-Baildon Mv, Maecker B, Schultze J, Gribben JG (2004) CD40 activation: potential for specific immunotherapy in B-CLL. Ann Oncol 15: 853–857.
• Zhou M, Gu L, Holden J, Yeager AM, Findley HW (2000) CD40 ligand upregulates expression of the IL-3 receptor and stimulates proliferation of B-lineage acute lymphoblastic leukemia cells in the presence of IL-3. Leukemia 14: 403–411.