NK cells restrain spontaneous antitumor CD8+ T cell priming through pd-1/pd-l1 interactions with dendritic cells
Despite the classical function of NK cells in the elimination of tumor and of virus-infected cells, evidence for a regulatory role for NK cells has been emerging in different models of autoimmunity, transplantation, and viral infections. However, this role has not been fully explored in the context...
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2016
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v197_n3_p953_RaffoIraolagoitia http://hdl.handle.net/20.500.12110/paper_00221767_v197_n3_p953_RaffoIraolagoitia |
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paper:paper_00221767_v197_n3_p953_RaffoIraolagoitia2023-06-08T14:46:58Z NK cells restrain spontaneous antitumor CD8+ T cell priming through pd-1/pd-l1 interactions with dendritic cells Ziblat, Andrea Domaica, Carolina Inés Fuertes, Mercedes Beatriz gamma interferon programmed death 1 ligand 1 programmed death 1 receptor tumor antigen Pdcd1 protein, mouse programmed death 1 ligand 1 programmed death 1 receptor animal cell animal experiment animal model animal tissue Article CD8+ T lymphocyte controlled study cross presentation cytokine production cytotoxicity dendritic cell effector cell human human cell lymph node mouse natural killer cell nonhuman phenotype priority journal protein expression protein protein interaction T lymphocyte subpopulation tumor growth tumor immunity upregulation animal C57BL mouse CD8+ T lymphocyte cell separation cross presentation dendritic cell experimental neoplasm flow cytometry immunology lymphocyte activation natural killer cell real time polymerase chain reaction signal transduction tumor cell line Animals Antigens, CD274 CD8-Positive T-Lymphocytes Cell Line, Tumor Cell Separation Cross-Priming Dendritic Cells Flow Cytometry Humans Killer Cells, Natural Lymphocyte Activation Mice Mice, Inbred C57BL Neoplasms, Experimental Programmed Cell Death 1 Receptor Real-Time Polymerase Chain Reaction Signal Transduction Despite the classical function of NK cells in the elimination of tumor and of virus-infected cells, evidence for a regulatory role for NK cells has been emerging in different models of autoimmunity, transplantation, and viral infections. However, this role has not been fully explored in the context of a growing tumor. In this article, we show that NK cells can limit spontaneous cross-priming of tumor Ag-specific CD8+ T cells, leading to reduced memory responses. After challenge with MC57 cells transduced to express the model Ag SIY (MC57.SIY), NK cell-depleted mice exhibited a significantly higher frequency of SIY-specific CD8+ T cells, with enhanced IFN-γ production and cytotoxic capability. Depletion of NK cells resulted in a CD8+ T cell population skewed toward an effector memory T phenotype that was associated with enhanced recall responses and delayed tumor growth after a secondary tumor challenge with B16.SIY cells. Dendritic cells (DCs) from NK cell-depleted tumor-bearing mice exhibited a more mature phenotype. Interestingly, tumor-infiltrating and tumor-draining lymph node NK cells displayed an upregulated expression of the inhibitory molecule programmed death ligand 1 that, through interaction with programmed death-1 expressed on DCs, limited DC activation, explaining their reduced ability to induce tumor-specific CD8+ T cell priming. Our results suggest that NK cells can, in certain contexts, have an inhibitory effect on antitumor immunity, a finding with implications for immunotherapy in the clinic. Copyright © 2016 by The American Association of Immunologists, Inc. Fil:Ziblat, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Domaica, C.I. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fuertes, M.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v197_n3_p953_RaffoIraolagoitia http://hdl.handle.net/20.500.12110/paper_00221767_v197_n3_p953_RaffoIraolagoitia |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
gamma interferon programmed death 1 ligand 1 programmed death 1 receptor tumor antigen Pdcd1 protein, mouse programmed death 1 ligand 1 programmed death 1 receptor animal cell animal experiment animal model animal tissue Article CD8+ T lymphocyte controlled study cross presentation cytokine production cytotoxicity dendritic cell effector cell human human cell lymph node mouse natural killer cell nonhuman phenotype priority journal protein expression protein protein interaction T lymphocyte subpopulation tumor growth tumor immunity upregulation animal C57BL mouse CD8+ T lymphocyte cell separation cross presentation dendritic cell experimental neoplasm flow cytometry immunology lymphocyte activation natural killer cell real time polymerase chain reaction signal transduction tumor cell line Animals Antigens, CD274 CD8-Positive T-Lymphocytes Cell Line, Tumor Cell Separation Cross-Priming Dendritic Cells Flow Cytometry Humans Killer Cells, Natural Lymphocyte Activation Mice Mice, Inbred C57BL Neoplasms, Experimental Programmed Cell Death 1 Receptor Real-Time Polymerase Chain Reaction Signal Transduction |
| spellingShingle |
gamma interferon programmed death 1 ligand 1 programmed death 1 receptor tumor antigen Pdcd1 protein, mouse programmed death 1 ligand 1 programmed death 1 receptor animal cell animal experiment animal model animal tissue Article CD8+ T lymphocyte controlled study cross presentation cytokine production cytotoxicity dendritic cell effector cell human human cell lymph node mouse natural killer cell nonhuman phenotype priority journal protein expression protein protein interaction T lymphocyte subpopulation tumor growth tumor immunity upregulation animal C57BL mouse CD8+ T lymphocyte cell separation cross presentation dendritic cell experimental neoplasm flow cytometry immunology lymphocyte activation natural killer cell real time polymerase chain reaction signal transduction tumor cell line Animals Antigens, CD274 CD8-Positive T-Lymphocytes Cell Line, Tumor Cell Separation Cross-Priming Dendritic Cells Flow Cytometry Humans Killer Cells, Natural Lymphocyte Activation Mice Mice, Inbred C57BL Neoplasms, Experimental Programmed Cell Death 1 Receptor Real-Time Polymerase Chain Reaction Signal Transduction Ziblat, Andrea Domaica, Carolina Inés Fuertes, Mercedes Beatriz NK cells restrain spontaneous antitumor CD8+ T cell priming through pd-1/pd-l1 interactions with dendritic cells |
| topic_facet |
gamma interferon programmed death 1 ligand 1 programmed death 1 receptor tumor antigen Pdcd1 protein, mouse programmed death 1 ligand 1 programmed death 1 receptor animal cell animal experiment animal model animal tissue Article CD8+ T lymphocyte controlled study cross presentation cytokine production cytotoxicity dendritic cell effector cell human human cell lymph node mouse natural killer cell nonhuman phenotype priority journal protein expression protein protein interaction T lymphocyte subpopulation tumor growth tumor immunity upregulation animal C57BL mouse CD8+ T lymphocyte cell separation cross presentation dendritic cell experimental neoplasm flow cytometry immunology lymphocyte activation natural killer cell real time polymerase chain reaction signal transduction tumor cell line Animals Antigens, CD274 CD8-Positive T-Lymphocytes Cell Line, Tumor Cell Separation Cross-Priming Dendritic Cells Flow Cytometry Humans Killer Cells, Natural Lymphocyte Activation Mice Mice, Inbred C57BL Neoplasms, Experimental Programmed Cell Death 1 Receptor Real-Time Polymerase Chain Reaction Signal Transduction |
| description |
Despite the classical function of NK cells in the elimination of tumor and of virus-infected cells, evidence for a regulatory role for NK cells has been emerging in different models of autoimmunity, transplantation, and viral infections. However, this role has not been fully explored in the context of a growing tumor. In this article, we show that NK cells can limit spontaneous cross-priming of tumor Ag-specific CD8+ T cells, leading to reduced memory responses. After challenge with MC57 cells transduced to express the model Ag SIY (MC57.SIY), NK cell-depleted mice exhibited a significantly higher frequency of SIY-specific CD8+ T cells, with enhanced IFN-γ production and cytotoxic capability. Depletion of NK cells resulted in a CD8+ T cell population skewed toward an effector memory T phenotype that was associated with enhanced recall responses and delayed tumor growth after a secondary tumor challenge with B16.SIY cells. Dendritic cells (DCs) from NK cell-depleted tumor-bearing mice exhibited a more mature phenotype. Interestingly, tumor-infiltrating and tumor-draining lymph node NK cells displayed an upregulated expression of the inhibitory molecule programmed death ligand 1 that, through interaction with programmed death-1 expressed on DCs, limited DC activation, explaining their reduced ability to induce tumor-specific CD8+ T cell priming. Our results suggest that NK cells can, in certain contexts, have an inhibitory effect on antitumor immunity, a finding with implications for immunotherapy in the clinic. Copyright © 2016 by The American Association of Immunologists, Inc. |
| author |
Ziblat, Andrea Domaica, Carolina Inés Fuertes, Mercedes Beatriz |
| author_facet |
Ziblat, Andrea Domaica, Carolina Inés Fuertes, Mercedes Beatriz |
| author_sort |
Ziblat, Andrea |
| title |
NK cells restrain spontaneous antitumor CD8+ T cell priming through pd-1/pd-l1 interactions with dendritic cells |
| title_short |
NK cells restrain spontaneous antitumor CD8+ T cell priming through pd-1/pd-l1 interactions with dendritic cells |
| title_full |
NK cells restrain spontaneous antitumor CD8+ T cell priming through pd-1/pd-l1 interactions with dendritic cells |
| title_fullStr |
NK cells restrain spontaneous antitumor CD8+ T cell priming through pd-1/pd-l1 interactions with dendritic cells |
| title_full_unstemmed |
NK cells restrain spontaneous antitumor CD8+ T cell priming through pd-1/pd-l1 interactions with dendritic cells |
| title_sort |
nk cells restrain spontaneous antitumor cd8+ t cell priming through pd-1/pd-l1 interactions with dendritic cells |
| publishDate |
2016 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v197_n3_p953_RaffoIraolagoitia http://hdl.handle.net/20.500.12110/paper_00221767_v197_n3_p953_RaffoIraolagoitia |
| work_keys_str_mv |
AT ziblatandrea nkcellsrestrainspontaneousantitumorcd8tcellprimingthroughpd1pdl1interactionswithdendriticcells AT domaicacarolinaines nkcellsrestrainspontaneousantitumorcd8tcellprimingthroughpd1pdl1interactionswithdendriticcells AT fuertesmercedesbeatriz nkcellsrestrainspontaneousantitumorcd8tcellprimingthroughpd1pdl1interactionswithdendriticcells |
| _version_ |
1768546287214395392 |