Artículo

Raffo Iraolagoitia, X.L.; Spallanzani, R.G.; Torres, N.I.; Araya, R.E.; Ziblat, A.; Domaica, C.I.; Sierra, J.M.; Nuñez, S.Y.; Secchiari, F.; Gajewski, T.F.; Zwirner, N.W.; Fuertes, M.B. "NK cells restrain spontaneous antitumor CD8+ T cell priming through pd-1/pd-l1 interactions with dendritic cells" (2016) Journal of Immunology. 197(3):953-961
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Abstract:

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.

Registro:

Documento: Artículo
Título:NK cells restrain spontaneous antitumor CD8+ T cell priming through pd-1/pd-l1 interactions with dendritic cells
Autor:Raffo Iraolagoitia, X.L.; Spallanzani, R.G.; Torres, N.I.; Araya, R.E.; Ziblat, A.; Domaica, C.I.; Sierra, J.M.; Nuñez, S.Y.; Secchiari, F.; Gajewski, T.F.; Zwirner, N.W.; Fuertes, M.B.
Filiación:Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, Ciudad de Buenos Aires, C1428ADN, Argentina
Department of Pathology, University of Chicago, Chicago, IL 60637, United States
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, United States
Departamento de Microbioloǵa, Parasitoloǵa e Inmunoloǵa, Facultad de Medicina, Universidad de Buenos Aires, Ciudad de Buenos Aires, C1121ABG, Argentina
Departamento de Qúmica Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina
Palabras clave: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
Año:2016
Volumen:197
Número:3
Página de inicio:953
Página de fin:961
DOI: http://dx.doi.org/10.4049/jimmunol.1502291
Título revista:Journal of Immunology
Título revista abreviado:J. Immunol.
ISSN:00221767
CODEN:JOIMA
CAS:gamma interferon, 82115-62-6; Antigens, CD274; Pdcd1 protein, mouse; Programmed Cell Death 1 Receptor
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v197_n3_p953_RaffoIraolagoitia

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Citas:

---------- APA ----------
Raffo Iraolagoitia, X.L., Spallanzani, R.G., Torres, N.I., Araya, R.E., Ziblat, A., Domaica, C.I., Sierra, J.M.,..., Fuertes, M.B. (2016) . NK cells restrain spontaneous antitumor CD8+ T cell priming through pd-1/pd-l1 interactions with dendritic cells. Journal of Immunology, 197(3), 953-961.
http://dx.doi.org/10.4049/jimmunol.1502291
---------- CHICAGO ----------
Raffo Iraolagoitia, X.L., Spallanzani, R.G., Torres, N.I., Araya, R.E., Ziblat, A., Domaica, C.I., et al. "NK cells restrain spontaneous antitumor CD8+ T cell priming through pd-1/pd-l1 interactions with dendritic cells" . Journal of Immunology 197, no. 3 (2016) : 953-961.
http://dx.doi.org/10.4049/jimmunol.1502291
---------- MLA ----------
Raffo Iraolagoitia, X.L., Spallanzani, R.G., Torres, N.I., Araya, R.E., Ziblat, A., Domaica, C.I., et al. "NK cells restrain spontaneous antitumor CD8+ T cell priming through pd-1/pd-l1 interactions with dendritic cells" . Journal of Immunology, vol. 197, no. 3, 2016, pp. 953-961.
http://dx.doi.org/10.4049/jimmunol.1502291
---------- VANCOUVER ----------
Raffo Iraolagoitia, X.L., Spallanzani, R.G., Torres, N.I., Araya, R.E., Ziblat, A., Domaica, C.I., et al. NK cells restrain spontaneous antitumor CD8+ T cell priming through pd-1/pd-l1 interactions with dendritic cells. J. Immunol. 2016;197(3):953-961.
http://dx.doi.org/10.4049/jimmunol.1502291