Idiotype-pulsed dendritic cells are able to induce antitumoral cytotoxic CD8 cells in chronic lymphocytic leukaemia
Françoise Vuillier,
Karim Maloum,
Elaine K. Thomas, Christian Magnac,
Gérard Dumas,
Béatrice Payelle-Brogard,
Pablo Oppezzo,
Guillaume Dighiero,
Daniel Scott-Algara,
Françoise Vuillier
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur,
Search for more papers by this authorKarim Maloum
Département d'Hématologie, Hôpital Pitié-Salpêtrière, Paris, France, and
Search for more papers by this authorChristian Magnac
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur,
Search for more papers by this authorGérard Dumas
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur,
Search for more papers by this authorBéatrice Payelle-Brogard
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur,
Search for more papers by this authorPablo Oppezzo
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur,
Search for more papers by this authorGuillaume Dighiero
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur,
Search for more papers by this authorDaniel Scott-Algara
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur,
Search for more papers by this authorFrançoise Vuillier,
Karim Maloum,
Elaine K. Thomas, Christian Magnac,
Gérard Dumas,
Béatrice Payelle-Brogard,
Pablo Oppezzo,
Guillaume Dighiero,
Daniel Scott-Algara,
Françoise Vuillier
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur,
Search for more papers by this authorKarim Maloum
Département d'Hématologie, Hôpital Pitié-Salpêtrière, Paris, France, and
Search for more papers by this authorChristian Magnac
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur,
Search for more papers by this authorGérard Dumas
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur,
Search for more papers by this authorBéatrice Payelle-Brogard
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur,
Search for more papers by this authorPablo Oppezzo
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur,
Search for more papers by this authorGuillaume Dighiero
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur,
Search for more papers by this authorDaniel Scott-Algara
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur,
Search for more papers by this authorFrançoise Vuillier, Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur, 28 rue du Dr Roux, F-75724 Paris Cedex 15, France. E-mail: [email protected]
Abstract
Summary. Idiotypic structures of immunoglobulins from malignant B cells constitute tumour-specific antigens, though the function of immunoglobulin-specific CD8+ T cells in disease control and rejection remains unclear. We have studied five cases of B chronic lymphocytic leukaemia patients affected with indolent (three patients) or aggressive (two patients) disease. We showed that CD8+ T cells with major histocompatibility complex class I-restricted cytotoxicity against autologous tumour B cells could be generated following repeated stimulations with idiotype-pulsed dendritic cells in vitro. CD8+ T-cell lines were able to upregulate CD69 expression and to release interferon (IFN)-γ upon contact with the autologous B cells, though cytolytic activity was only substantiated for patients with indolent disease. The failure of cytolytic activity in patients with aggressive disease may be explained by a skewed maturation of memory CD8 cells.
References
- Bannerji, R. & Byrd, J.C. (2000) Update on the biology of chronic lymphocytic leukemia. Current Opinion in Oncology, 12, 22–29.
- Bendandi, M., Gocke, C.D., Kobrin, C.B., Benko, F.A., Sternas, L.A., Pennington, R., Watson, T.M., Reynolds, C.W., Gause, B.L., Duffey, P.L., Jaffe, E.S., Creekmore, S.P., Longo, D.L. & Kwak, L.W. (1999) Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma. Nature Medicine, 5, 1171–1177.
- Bojarska-Junak, A., Rolinski, J., Wasik-Szczepaneko, E., Kaluzny, Z. & Dmoszynska, A. (2002) Intracellular tumor necrosis factor production by T- and B-cells in B-cell chronic lymphocytic leukemia. Haematologica, 87, 490–499.
- Buhmann, R., Nolte, A., Westhaus, D., Emmerich, B. & Hallek, M. (1999) CD40-activated B-cell chronic lymphocytic leukemia cells for tumor immunotherapy: stimulation of allogeneic versus autologous T cells generates different types of effector cells. Blood, 93, 1992–2002.
- Caligaris-Cappio, F. & Hamblin, T.J. (1999) B-cell chronic lymphocytic leukemia: a bird of a different feather. Journal of Clinical Oncology, 17, 399–408.
- Champagne, P., Ogg, G.S., King, A.S., Knabenhans, C., Ellefsen, K., Nobile, M., Appay, V., Rizzardi, G.P., Fleury, S., Lipp, M., Forster, R., Rowland-Jones, S., Sekaly, R.P., McMichael, A.J. & Pantaleo, G. (2001) Skewed maturation of memory HIV-specific CD8 T lymphocytes. Nature, 410, 106–111.
-
Chaux, P.,
Vantomme, V.,
Coulie, P.,
Boon, T. &
Van Der Bruggen, P. (1998) Estimation of the frequencies of anti-MAGE-3 cytolytic T-lymphocyte precursors in blood from individuals without cancer.
International Journal of Cancer, 77, 538–542.
10.1002/(SICI)1097-0215(19980812)77:4<538::AID-IJC11>3.0.CO;2-2 CAS PubMed Web of Science® Google Scholar
- Cull, G., Durrant, L., Stainer, C., Haynes, A. & Russell, N. (1999) Generation of anti-idiotype immune responses following vaccination with idiotype-protein pulsed dendritic cells in myeloma. British Journal of Haematology, 107, 648–655.
- Dighiero, G. & Binet, J.L. (2000) When and how to treat chronic lymphocytic leukemia. New England Journal of Medicine, 343, 1799–1801.
- Dumas, G., Pritsch, O., Pereira, A., Gallart, T. & Dighiero, G. (1997) A murine model of human cold agglutinin disease. British Journal of Haematology, 98, 589–596.
- Goddard, R.V., Prentice, A.G., Copplestone, J.A. & Kaminski, E.R. (2001) Generation in vitro of B-cell chronic lymphocytic leukaemia-proliferative and specific HLA class-II-restricted cytotoxic T-cell responses using autologous dendritic cells pulsed with tumour cell lysate. Clinical and Experimental Immunology, 126, 16–28.
- Granziero, L., Ghia, P., Circosta, P., Gottardi, D., Strola, G., Geuna, M., Montagna, L., Piccoli, P., Chilosi, M. & Caligaris-Cappio, F. (2001) Survivin is expressed on CD40 stimulation and interfaces proliferation and apoptosis in B-cell chronic lymphocytic leukemia. Blood, 97, 2777–2783.
- Gricks, C.S., Rawlings, E., Foroni, L., Madrigal, J.A. & Amlot, P.L. (2001) Somatically mutated regions of immunoglobulin on human B-cell lymphomas code for peptides that bind to autologous major histocompatibility complex class I, providing a potential target for cytotoxic T cells. Cancer Research, 61, 5145–5152.
- He, X.S., Rehermann, B., Lopez-Labrador, F.X., Boisvert, J., Cheung, R., Mumm, J., Wedemeyer, H., Berenguer, M., Wright, T.L., Davis, M.M. & Greenberg, H.B. (1999) Quantitative analysis of hepatitis C virus-specific CD8(+) T cells in peripheral blood and liver using peptide-MHC tetramers. Proceedings of the National Academy of Sciences of the United States of America, 96, 5692–5697.
- Hislop, A.D., Gudgeon, N.H., Callan, M.F., Fazou, C., Hasegawa, H., Salmon, M. & Rickinson, A.B. (2001) EBV-specific CD8+ T cell memory: relationships between epitope specificity, cell phenotype, and immediate effector function. Journal of Immunology, 167, 2019–2029.
- Hsu, F.J., Benike, C., Fagnoni, F., Liles, T.M., Czerwinski, D., Taidi, B., Engleman, E.G. & Levy, R. (1996) Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nature Medicine, 2, 52–58.
- Hsu, F.J., Caspar, C.B., Czerwinski, D., Kwak, L.W., Liles, T.M., Syrengelas, A., Taidi-Laskowski, B. & Levy, R. (1997) Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma: long-term results of a clinical trial. Blood, 89, 3129–3135.
- Kwak, L.W., Campbell, M.J., Czerwinski, D.K., Hart, S., Miller, R.A. & Levy, R. (1992) Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors. New England Journal of Medicine, 327, 1209–1215.
- Matutes, E., Owusu-Ankomah, K., Morilla, R., Garcia Marco, J., Houlihan, A., Que, T.H. & Catovsky, D. (1994) The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia, 8, 1640–1645.
- Mosca, P.J., Hobeika, A.C., Clay, T.M., Nair, S.K., Thomas, E.K., Morse, M.A. & Lyerly, H.K. (2000) A subset of human monocyte-derived dendritic cells expresses high levels of interleukin-12 in response to combined CD40 ligand and interferon-gamma treatment. Blood, 96, 3499–3504.
- Nelson, E.L., Li, X., Hsu, F.J., Kwak, L.W., Levy, R., Clayberger, C. & Krensky, A.M. (1996) Tumor-specific, cytotoxic T-lymphocyte response after idiotype vaccination for B-cell, non-Hodgkin's lymphoma. Blood, 88, 580–589.
- Osterroth, F., Garbe, A., Fisch, P. & Veelken, H. (2000) Stimulation of cytotoxic T cells against idiotype immunoglobulin of malignant lymphoma with protein-pulsed or idiotype-transduced dendritic cells. Blood, 95, 1342–1349.
- Pritsch, O., Magnac, C., Dumas, G., Egile, C. & Dighiero, G. (1993) V gene usage by seven hybrids derived from CD5+ B-cell chronic lymphocytic leukemia and displaying autoantibody activity. Blood, 82, 3103–3112.
- Reid, D.C. (2001) Dendritic cells and immunotherapy for malignant disease. British Journal of Haematology, 112, 874–887.
- Rezvany, M.R., Jeddi-Tehrani, M., Rabbani, H., Lewin, N., Avila-Carino, J., Osterborg, A., Wigzell, H. & Mellstedt, H. (2000) Autologous T lymphocytes may specifically recognize leukaemic B cells in patients with chronic lymphocytic leukaemia. British Journal of Haematology, 111, 608–617.
- Rezvany, M.R., Jeddi-Tehrani, M., Biberfeld, P., Soderlund, J., Mellstedt, H., Osterborg, A. & Rabbani, H. (2001) Dendritic cells in patients with non-progressive B-chronic lymphocytic leukaemia have a normal functional capability but abnormal cytokine pattern. British Journal of Haematology, 115, 263–271.
- Sallusto, F. & Lanzavecchia, A. (2001) Exploring pathways for memory T cell generation. Journal of Clinical Investigation, 108, 805–806.
- Shimoni, A., Marcus, H., Dekel, B., Shkarchi, R., Arditti, F., Shvidel, L., Shtalrid, M., Bucher, W., Canaan, A., Ergas, D., Berrebi, A. & Reisner, Y. (1999) Autologous T cells control B-chronic lymphocytic leukemia tumor progression in human→mouse radiation chimera. Cancer Research, 59, 5968–5974.
- Staveley-O'Carroll, K., Sotomayor, E., Montgomery, J., Borrello, I., Hwang, L., Fein, S., Pardoll, D. & Levitsky, H. (1998) Induction of antigen-specific T cell anergy: an early event in the course of tumor progression. Proceedings of the National Academy of Sciences of the United States of America, 95, 1178–1183.
- Titzer, S., Christensen, O., Manzke, O., Tesch, H., Wolf, J., Emmerich, B., Carsten, C., Diehl, V. & Bohlen, H. (2000) Vaccination of multiple myeloma patients with idiotype-pulsed dendritic cells: immunological and clinical aspects. British Journal of Haematology, 108, 805–816.
- Trojan, A., Schultze, J.L., Witzens, M., Vonderheide, R.H., Ladetto, M., Donovan, J.W. & Gribben, J.G. (2000) Immunoglobulin framework-derived peptides function as cytotoxic T-cell epitopes commonly expressed in B-cell malignancies. Nature Medicine, 6, 667–672.
- Vuillier, F., Maloum, K., Thomas, E.K., Jouanne, C., Dighiero, G. & Scott-Algara, D. (2001) Functional monocyte-derived dendritic cells can be generated in chronic lymphocytic leukaemia. British Journal of Haematology, 115, 831–844.
- Wen, Y.J., Min, R., Tricot, G., Barlogie, B. & Yi, Q. (2002) Tumor lysate-specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy. Blood, 99, 3280–3285.
Citing Literature
