PMID- 27342842
OWN - NLM
STAT- MEDLINE
DCOM- 20170808
LR  - 20220316
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 197
IP  - 3
DP  - 2016 Aug 1
TI  - NK Cells Restrain Spontaneous Antitumor CD8+ T Cell Priming through PD-1/PD-L1 
      Interactions with Dendritic Cells.
PG  - 953-61
LID - 10.4049/jimmunol.1502291 [doi]
AB  - 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-gamma 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.
CI  - Copyright (c) 2016 by The American Association of Immunologists, Inc.
FAU - Iraolagoitia, Ximena L Raffo
AU  - Iraolagoitia XL
AUID- ORCID: 0000-0002-8891-4821
AD  - Laboratorio de Fisiopatologia de la Inmunidad Innata, Instituto de Biologia y 
      Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y 
      Tecnicas, Ciudad de Buenos Aires C1428ADN, Argentina;
FAU - Spallanzani, Raul G
AU  - Spallanzani RG
AUID- ORCID: 0000-0001-5402-3687
AD  - Laboratorio de Fisiopatologia de la Inmunidad Innata, Instituto de Biologia y 
      Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y 
      Tecnicas, Ciudad de Buenos Aires C1428ADN, Argentina;
FAU - Torres, Nicolas I
AU  - Torres NI
AD  - Laboratorio de Fisiopatologia de la Inmunidad Innata, Instituto de Biologia y 
      Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y 
      Tecnicas, Ciudad de Buenos Aires C1428ADN, Argentina;
FAU - Araya, Romina E
AU  - Araya RE
AUID- ORCID: 0000-0001-9787-2670
AD  - Laboratorio de Fisiopatologia de la Inmunidad Innata, Instituto de Biologia y 
      Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y 
      Tecnicas, Ciudad de Buenos Aires C1428ADN, Argentina;
FAU - Ziblat, Andrea
AU  - Ziblat A
AD  - Laboratorio de Fisiopatologia de la Inmunidad Innata, Instituto de Biologia y 
      Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y 
      Tecnicas, Ciudad de Buenos Aires C1428ADN, Argentina;
FAU - Domaica, Carolina I
AU  - Domaica CI
AD  - Laboratorio de Fisiopatologia de la Inmunidad Innata, Instituto de Biologia y 
      Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y 
      Tecnicas, Ciudad de Buenos Aires C1428ADN, Argentina;
FAU - Sierra, Jessica M
AU  - Sierra JM
AD  - Laboratorio de Fisiopatologia de la Inmunidad Innata, Instituto de Biologia y 
      Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y 
      Tecnicas, Ciudad de Buenos Aires C1428ADN, Argentina;
FAU - Nunez, Sol Y
AU  - Nunez SY
AUID- ORCID: 0000-0002-7856-2973
AD  - Laboratorio de Fisiopatologia de la Inmunidad Innata, Instituto de Biologia y 
      Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y 
      Tecnicas, Ciudad de Buenos Aires C1428ADN, Argentina;
FAU - Secchiari, Florencia
AU  - Secchiari F
AD  - Laboratorio de Fisiopatologia de la Inmunidad Innata, Instituto de Biologia y 
      Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y 
      Tecnicas, Ciudad de Buenos Aires C1428ADN, Argentina;
FAU - Gajewski, Thomas F
AU  - Gajewski TF
AD  - Department of Pathology, The University of Chicago, Chicago, IL 60637; Section of 
      Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, 
      IL 60637;
FAU - Zwirner, Norberto W
AU  - Zwirner NW
AUID- ORCID: 0000-0001-7098-359X
AD  - Laboratorio de Fisiopatologia de la Inmunidad Innata, Instituto de Biologia y 
      Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y 
      Tecnicas, Ciudad de Buenos Aires C1428ADN, Argentina; Departamento de 
      Microbiologia, Parasitologia e Inmunologia, Facultad de Medicina, Universidad de 
      Buenos Aires, Ciudad de Buenos Aires C1121ABG, Argentina; and Departamento de 
      Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de 
      Buenos Aires, Buenos Aires C1428EGA, Argentina.
FAU - Fuertes, Mercedes B
AU  - Fuertes MB
AUID- ORCID: 0000-0002-2734-1468
AD  - Laboratorio de Fisiopatologia de la Inmunidad Innata, Instituto de Biologia y 
      Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y 
      Tecnicas, Ciudad de Buenos Aires C1428ADN, Argentina; Departamento de Quimica 
      Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 
      Buenos Aires C1428EGA, Argentina merfuer@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160624
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Pdcd1 protein, mouse)
RN  - 0 (Programmed Cell Death 1 Receptor)
SB  - IM
MH  - Animals
MH  - B7-H1 Antigen/immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Line, Tumor
MH  - Cell Separation
MH  - Cross-Priming/*immunology
MH  - Dendritic Cells/*immunology
MH  - Flow Cytometry
MH  - Humans
MH  - Killer Cells, Natural/*immunology
MH  - Lymphocyte Activation/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neoplasms, Experimental/*immunology
MH  - Programmed Cell Death 1 Receptor/immunology
MH  - Real-Time Polymerase Chain Reaction
MH  - Signal Transduction/immunology
EDAT- 2016/06/28 06:00
MHDA- 2017/08/09 06:00
CRDT- 2016/06/26 06:00
PHST- 2015/10/27 00:00 [received]
PHST- 2016/05/27 00:00 [accepted]
PHST- 2016/06/26 06:00 [entrez]
PHST- 2016/06/28 06:00 [pubmed]
PHST- 2017/08/09 06:00 [medline]
AID - jimmunol.1502291 [pii]
AID - 10.4049/jimmunol.1502291 [doi]
PST - ppublish
SO  - J Immunol. 2016 Aug 1;197(3):953-61. doi: 10.4049/jimmunol.1502291. Epub 2016 Jun 
      24.