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Abstract:

If irradiated tumor cells could be rendered immunogenic, they would provide a safe, broad, and patient-specific array of antigens for immunotherapies. Prior approaches have emphasized genetic transduction of live tumor cells to express cytokines, costimulators, and surrogate foreign antigens. We asked if immunity could be achieved by delivering irradiated, major histocompatibility complex-negative plasmacytoma cells to maturing mouse dendritic cells (DCs) within lymphoid organs. Tumor cells injected intravenously (i.v.) were captured by splenic DCs, whereas subcutaneous (s.c.) injection led only to weak uptake in lymph node or spleen. The natural killer T (NKT) cells mobilizing glycolipid α-galactosyl ceramide, used to mature splenic DCs, served as an effective adjuvant to induce protective immunity. This adjuvant function was mimicked by a combination of poly IC and agonistic αCD40 antibody. The adjuvant glycolipid had to be coadministered with tumor cells i.v. rather than s.c. Specific resistance was generated both to a plasmacytoma and lymphoma. The resistance afforded by a single vaccination lasted >2 mo and required both CD4+ and CD8+ T cells. Mature tumor capturing DCs stimulated the differentiation of P1A tumor antigen-specific, CD8+ T cells and uniquely transferred tumor resistance to naive mice. Therefore, the access of dying tumor cells to DCs that are maturing to activated NKT cells efficiently induces long-lived adaptive resistance. JEM © The Rockefeller University Press.

Registro:

Documento: Artículo
Título:Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells
Autor:Liu, K.; Idoyaga, J.; Charalambous, A.; Fujii, S.-I.; Bonito, A.; Mordoh, J.; Wainstok, R.; Bai, X.-F.; Liu, Y.; Steinman, R.M.
Filiación:Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021, United States
Instituto Leloir, Instituto de Investigaciones Bioquimicas, Universidad de Buenos Aires, 1650 Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, 1650 Buenos Aires, Argentina
Division of Cancer Immunology, Department of Pathology, Ohio State University Medical Center, Columbus, OH 43210, United States
Palabras clave:adjuvant; alpha CD40 antibody; alpha galactosylceramide; antibody; CD4 antigen; CD8 antigen; glycolipid; major histocompatibility antigen class 1; polyinosinic polycytidylic acid; tumor antigen; unclassified drug; animal cell; animal experiment; animal model; article; cell differentiation; cell maturation; controlled study; dendritic cell; drug delivery system; drug uptake; female; irradiation; lymph node; lymphoid organ; lymphoma; major histocompatibility complex; mouse; natural killer cell; nonhuman; plasmacytoma; priority journal; spleen; spleen cell; T lymphocyte; tumor immunity; tumor resistance; vaccination; Adjuvants, Immunologic; Animals; Antigen Presentation; Antigens, Neoplasm; Cancer Vaccines; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Differentiation; Dendritic Cells; Female; Gamma Rays; Immunotherapy, Active; Killer Cells, Natural; Lymph Nodes; Lymphocyte Activation; Lymphoma; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neoplasms, Experimental; Plasmacytoma; Spleen
Año:2005
Volumen:202
Número:11
Página de inicio:1507
Página de fin:1516
DOI: http://dx.doi.org/10.1084/jem.20050956
Título revista:Journal of Experimental Medicine
Título revista abreviado:J. Exp. Med.
ISSN:00221007
CODEN:JEMEA
CAS:polyinosinic polycytidylic acid, 24939-03-5, 26301-44-0; Adjuvants, Immunologic; Antigens, Neoplasm; Cancer Vaccines; tumor rejection antigen P815A, mouse
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00221007_v202_n11_p1507_Liu.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221007_v202_n11_p1507_Liu

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Citas:

---------- APA ----------
Liu, K., Idoyaga, J., Charalambous, A., Fujii, S.-I., Bonito, A., Mordoh, J., Wainstok, R.,..., Steinman, R.M. (2005) . Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells. Journal of Experimental Medicine, 202(11), 1507-1516.
http://dx.doi.org/10.1084/jem.20050956
---------- CHICAGO ----------
Liu, K., Idoyaga, J., Charalambous, A., Fujii, S.-I., Bonito, A., Mordoh, J., et al. "Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells" . Journal of Experimental Medicine 202, no. 11 (2005) : 1507-1516.
http://dx.doi.org/10.1084/jem.20050956
---------- MLA ----------
Liu, K., Idoyaga, J., Charalambous, A., Fujii, S.-I., Bonito, A., Mordoh, J., et al. "Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells" . Journal of Experimental Medicine, vol. 202, no. 11, 2005, pp. 1507-1516.
http://dx.doi.org/10.1084/jem.20050956
---------- VANCOUVER ----------
Liu, K., Idoyaga, J., Charalambous, A., Fujii, S.-I., Bonito, A., Mordoh, J., et al. Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells. J. Exp. Med. 2005;202(11):1507-1516.
http://dx.doi.org/10.1084/jem.20050956