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PI3K[gamma] is a molecular switch that controls immune suppression

Macrophages play critical, but opposite, roles in acute and chronic inflammation and cancer1-5. In response to pathogens or injury, inflammatory macrophages express cytokines that stimulate cytotoxic T cells, whereas macrophages in neoplastic and parasitic diseases express anti-inflammatory cytokine... Full description

Journal Title: Nature Nov 17, 2016, Vol.539(7629), pp.437-442N
Main Author: Kaneda, Megan
Other Authors: Messer, Karen , Ralainirina, Natacha , Li, Hongying , Leem, Christopher , Gorjestani, Sara , Woo, Gyunghwi , Nguyen, Abraham , Figueiredo, Camila , Foubert, Philippe , Schmid, Michael , Pink, Melissa , Winkler, David , Rausch, Matthew , Palombella, Vito , Kutok, Jeffery , Mcgovern, Karen , Frazer, Kelly , Wu, Xuefeng , Karin
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 00280836 ; E-ISSN: 14764687 ; DOI: 10.1038/nature19834
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title: PI3K[gamma] is a molecular switch that controls immune suppression
format: Article
creator:
  • Kaneda, Megan
  • Messer, Karen
  • Ralainirina, Natacha
  • Li, Hongying
  • Leem, Christopher
  • Gorjestani, Sara
  • Woo, Gyunghwi
  • Nguyen, Abraham
  • Figueiredo, Camila
  • Foubert, Philippe
  • Schmid, Michael
  • Pink, Melissa
  • Winkler, David
  • Rausch, Matthew
  • Palombella, Vito
  • Kutok, Jeffery
  • Mcgovern, Karen
  • Frazer, Kelly
  • Wu, Xuefeng
  • Karin
subjects:
  • Kinases
  • Human Papillomavirus
  • Proteins
  • Phosphorylation
  • Studies
  • Tumors
  • Cancer
  • Leucocytes
  • Cytokines
  • Deoxyribonucleic Acid–DNA
  • Genomes
  • Gene Expression
  • Inflammation
ispartof: Nature, Nov 17, 2016, Vol.539(7629), pp.437-442N
description: Macrophages play critical, but opposite, roles in acute and chronic inflammation and cancer1-5. In response to pathogens or injury, inflammatory macrophages express cytokines that stimulate cytotoxic T cells, whereas macrophages in neoplastic and parasitic diseases express anti-inflammatory cytokines that induce immune suppression and may promote resistance to T cell checkpoint inhibitors1-7. Here we show that macrophage PI 3-kinase [gamma] controls a critical switch between immune stimulation and suppression during inflammation and cancer. PI3K[gamma] signalling through Akt and mTOR inhibits NF[kappa]B activation while stimulating C/EBP[beta] activation, thereby inducing a transcriptional program that promotes immune suppression during inflammation and tumour growth. By contrast, selective inactivation of macrophage PI3K[gamma] stimulates and prolongs NF[kappa]B activation and inhibits C/EBP[beta] activation, thus promoting an immunostimulatory transcriptional program that restores CD8^sup...
language: eng
source:
identifier: ISSN: 00280836 ; E-ISSN: 14764687 ; DOI: 10.1038/nature19834
fulltext: fulltext
issn:
  • 00280836
  • 0028-0836
  • 14764687
  • 1476-4687
url: Link


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titlePI3K[gamma] is a molecular switch that controls immune suppression
creatorKaneda, Megan ; Messer, Karen ; Ralainirina, Natacha ; Li, Hongying ; Leem, Christopher ; Gorjestani, Sara ; Woo, Gyunghwi ; Nguyen, Abraham ; Figueiredo, Camila ; Foubert, Philippe ; Schmid, Michael ; Pink, Melissa ; Winkler, David ; Rausch, Matthew ; Palombella, Vito ; Kutok, Jeffery ; Mcgovern, Karen ; Frazer, Kelly ; Wu, Xuefeng ; Karin
ispartofNature, Nov 17, 2016, Vol.539(7629), pp.437-442N
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subjectKinases ; Human Papillomavirus ; Proteins ; Phosphorylation ; Studies ; Tumors ; Cancer ; Leucocytes ; Cytokines ; Deoxyribonucleic Acid–DNA ; Genomes ; Gene Expression ; Inflammation
descriptionMacrophages play critical, but opposite, roles in acute and chronic inflammation and cancer1-5. In response to pathogens or injury, inflammatory macrophages express cytokines that stimulate cytotoxic T cells, whereas macrophages in neoplastic and parasitic diseases express anti-inflammatory cytokines that induce immune suppression and may promote resistance to T cell checkpoint inhibitors1-7. Here we show that macrophage PI 3-kinase [gamma] controls a critical switch between immune stimulation and suppression during inflammation and cancer. PI3K[gamma] signalling through Akt and mTOR inhibits NF[kappa]B activation while stimulating C/EBP[beta] activation, thereby inducing a transcriptional program that promotes immune suppression during inflammation and tumour growth. By contrast, selective inactivation of macrophage PI3K[gamma] stimulates and prolongs NF[kappa]B activation and inhibits C/EBP[beta] activation, thus promoting an immunostimulatory transcriptional program that restores CD8^sup...
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titlePI3K[gamma] is a molecular switch that controls immune suppression
descriptionMacrophages play critical, but opposite, roles in acute and chronic inflammation and cancer1-5. In response to pathogens or injury, inflammatory macrophages express cytokines that stimulate cytotoxic T cells, whereas macrophages in neoplastic and parasitic diseases express anti-inflammatory cytokines that induce immune suppression and may promote resistance to T cell checkpoint inhibitors1-7. Here we show that macrophage PI 3-kinase [gamma] controls a critical switch between immune stimulation and suppression during inflammation and cancer. PI3K[gamma] signalling through Akt and mTOR inhibits NF[kappa]B activation while stimulating C/EBP[beta] activation, thereby inducing a transcriptional program that promotes immune suppression during inflammation and tumour growth. By contrast, selective inactivation of macrophage PI3K[gamma] stimulates and prolongs NF[kappa]B activation and inhibits C/EBP[beta] activation, thus promoting an immunostimulatory transcriptional program that restores CD8^sup...
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citationpf 437 pt 442N vol 539 issue 7629
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titlePI3K[gamma] is a molecular switch that controls immune suppression
authorKaneda, Megan ; Messer, Karen ; Ralainirina, Natacha ; Li, Hongying ; Leem, Christopher ; Gorjestani, Sara ; Woo, Gyunghwi ; Nguyen, Abraham ; Figueiredo, Camila ; Foubert, Philippe ; Schmid, Michael ; Pink, Melissa ; Winkler, David ; Rausch, Matthew ; Palombella, Vito ; Kutok, Jeffery ; Mcgovern, Karen ; Frazer, Kelly ; Wu, Xuefeng ; Karin
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abstractMacrophages play critical, but opposite, roles in acute and chronic inflammation and cancer1-5. In response to pathogens or injury, inflammatory macrophages express cytokines that stimulate cytotoxic T cells, whereas macrophages in neoplastic and parasitic diseases express anti-inflammatory cytokines that induce immune suppression and may promote resistance to T cell checkpoint inhibitors1-7. Here we show that macrophage PI 3-kinase [gamma] controls a critical switch between immune stimulation and suppression during inflammation and cancer. PI3K[gamma] signalling through Akt and mTOR inhibits NF[kappa]B activation while stimulating C/EBP[beta] activation, thereby inducing a transcriptional program that promotes immune suppression during inflammation and tumour growth. By contrast, selective inactivation of macrophage PI3K[gamma] stimulates and prolongs NF[kappa]B activation and inhibits C/EBP[beta] activation, thus promoting an immunostimulatory transcriptional program that restores CD8^sup...
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date2016-11-17