Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells
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 ask...
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todo:paper_00221007_v202_n11_p1507_Liu2023-10-03T14:26:23Z Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells Liu, K. Idoyaga, J. Charalambous, A. Fujii, S.-I. Bonito, A. Mordoh, J. Wainstok, R. Bai, X.-F. Liu, Y. Steinman, R.M. 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 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. Fil:Idoyaga, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00221007_v202_n11_p1507_Liu |
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Universidad de Buenos Aires |
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I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Liu, K. Idoyaga, J. Charalambous, A. Fujii, S.-I. Bonito, A. Mordoh, J. Wainstok, R. Bai, X.-F. Liu, Y. Steinman, R.M. Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Liu, K. Idoyaga, J. Charalambous, A. Fujii, S.-I. Bonito, A. Mordoh, J. Wainstok, R. Bai, X.-F. Liu, Y. Steinman, R.M. |
| author_facet |
Liu, K. Idoyaga, J. Charalambous, A. Fujii, S.-I. Bonito, A. Mordoh, J. Wainstok, R. Bai, X.-F. Liu, Y. Steinman, R.M. |
| author_sort |
Liu, K. |
| title |
Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells |
| title_short |
Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells |
| title_full |
Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells |
| title_fullStr |
Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells |
| title_full_unstemmed |
Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells |
| title_sort |
innate nkt lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells |
| url |
http://hdl.handle.net/20.500.12110/paper_00221007_v202_n11_p1507_Liu |
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