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Phenotypically distinct helper NK cells are required for gp96-mediated anti-tumor immunity.

A number of Heat Shock Proteins (HSPs), in the extracellular environment, are immunogenic. Following cross-presentation of HSP-chaperoned peptides by CD91(+) antigen presenting cells (APCs), T cells are primed with specificity for the derivative antigen-bearing cell. Accordingly, tumor-derived HSPs... Full description

Journal Title: Scientific reports July 19, 2016, Vol.6, p.29889
Main Author: Sedlacek, Abigail L
Other Authors: Kinner-Bibeau, Lauren B , Binder, Robert J
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 2045-2322 ; DOI: 10.1038/srep29889
Link: http://search.proquest.com/docview/1805758252/?pq-origsite=primo
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title: Phenotypically distinct helper NK cells are required for gp96-mediated anti-tumor immunity.
format: Article
creator:
  • Sedlacek, Abigail L
  • Kinner-Bibeau, Lauren B
  • Binder, Robert J
subjects:
  • Antigen-Presenting Cells–Immunology
  • Antigens, Neoplasm–Immunology
  • Cross-Priming–Immunology
  • Heat-Shock Proteins–Immunology
  • Humans–Therapeutic Use
  • Immunity, Cellular–Immunology
  • Interleukin-2–Immunology
  • Killer Cells, Natural–Immunology
  • Low Density Lipoprotein Receptor-Related Protein-1–Immunology
  • Membrane Glycoproteins–Immunology
  • Molecular Chaperones–Therapeutic Use
  • Peptides–Immunology
  • T-Lymphocytes–Immunology
  • T-Lymphocytes, Helper-Inducer–Immunology
  • Antigens, Neoplasm
  • Heat-Shock Proteins
  • Interleukin-2
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Membrane Glycoproteins
  • Molecular Chaperones
  • Peptides
  • Endoplasmin
ispartof: Scientific reports, July 19, 2016, Vol.6, p.29889
description: A number of Heat Shock Proteins (HSPs), in the extracellular environment, are immunogenic. Following cross-presentation of HSP-chaperoned peptides by CD91(+) antigen presenting cells (APCs), T cells are primed with specificity for the derivative antigen-bearing cell. Accordingly, tumor-derived HSPs are in clinical trials for cancer immunotherapy. We investigate the role of NK cells in gp96-mediated anti-tumor immune responses given their propensity to lyse tumor cells. We show that gp96-mediated rejection of tumors requires a unique and necessary helper role in NK cells. This helper role occurs during the effector phase of the anti-tumor immune response and is required for T cell and APC function. Gp96 activates NK cells indirectly via APCs to a phenotype distinct from NK cells activated by other mechanisms such as IL-2. While NK cells have both lytic and cytokine producing properties, we show that gp96 selectively activates cytokine production in NK cells, which is important in the HSP anti-tumor immune response, and leaves their cytotoxic capacity unchanged.
language: eng
source:
identifier: E-ISSN: 2045-2322 ; DOI: 10.1038/srep29889
fulltext: fulltext
issn:
  • 20452322
  • 2045-2322
url: Link


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titlePhenotypically distinct helper NK cells are required for gp96-mediated anti-tumor immunity.
creatorSedlacek, Abigail L ; Kinner-Bibeau, Lauren B ; Binder, Robert J
contributorSedlacek, Abigail L (correspondence author) ; Sedlacek, Abigail L (record owner)
ispartofScientific reports, July 19, 2016, Vol.6, p.29889
identifierE-ISSN: 2045-2322 ; DOI: 10.1038/srep29889
subjectAntigen-Presenting Cells–Immunology ; Antigens, Neoplasm–Immunology ; Cross-Priming–Immunology ; Heat-Shock Proteins–Immunology ; Humans–Therapeutic Use ; Immunity, Cellular–Immunology ; Interleukin-2–Immunology ; Killer Cells, Natural–Immunology ; Low Density Lipoprotein Receptor-Related Protein-1–Immunology ; Membrane Glycoproteins–Immunology ; Molecular Chaperones–Therapeutic Use ; Peptides–Immunology ; T-Lymphocytes–Immunology ; T-Lymphocytes, Helper-Inducer–Immunology ; Antigens, Neoplasm ; Heat-Shock Proteins ; Interleukin-2 ; Low Density Lipoprotein Receptor-Related Protein-1 ; Membrane Glycoproteins ; Molecular Chaperones ; Peptides ; Endoplasmin
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descriptionA number of Heat Shock Proteins (HSPs), in the extracellular environment, are immunogenic. Following cross-presentation of HSP-chaperoned peptides by CD91(+) antigen presenting cells (APCs), T cells are primed with specificity for the derivative antigen-bearing cell. Accordingly, tumor-derived HSPs are in clinical trials for cancer immunotherapy. We investigate the role of NK cells in gp96-mediated anti-tumor immune responses given their propensity to lyse tumor cells. We show that gp96-mediated rejection of tumors requires a unique and necessary helper role in NK cells. This helper role occurs during the effector phase of the anti-tumor immune response and is required for T cell and APC function. Gp96 activates NK cells indirectly via APCs to a phenotype distinct from NK cells activated by other mechanisms such as IL-2. While NK cells have both lytic and cytokine producing properties, we show that gp96 selectively activates cytokine production in NK cells, which is important in the HSP anti-tumor immune response, and leaves their cytotoxic capacity unchanged.
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