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miR-155 augments CD8+ T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γc cytokines

Lymphodepleting regimens are used before adoptive immunotherapy to augment the antitumor efficacy of transferred T cells by removing endogenous homeostatic "cytokine sinks." These conditioning modalities, however, are often associated with severe toxicities. We found that microRNA-155 (miR-155) enab... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America 13 January 2015, Vol.112(2), pp.476-81
Main Author: Ji, Yun
Other Authors: Wrzesinski, Claudia , Yu, Zhiya , Hu, Jinhui , Gautam, Sanjivan , Hawk, Nga V , Telford, William G , Palmer, Douglas C , Franco, Zulmarie , Sukumar, Madhusudhanan , Roychoudhuri, Rahul , Clever, David , Klebanoff, Christopher A , Surh, Charles D , Waldmann, Thomas A , Restifo, Nicholas P , Gattinoni, Luca
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1091-6490 ; PMID: 25548153 Version:1 ; DOI: 10.1073/pnas.1422916112
Link: http://pubmed.gov/25548153
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title: miR-155 augments CD8+ T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γc cytokines
format: Article
creator:
  • Ji, Yun
  • Wrzesinski, Claudia
  • Yu, Zhiya
  • Hu, Jinhui
  • Gautam, Sanjivan
  • Hawk, Nga V
  • Telford, William G
  • Palmer, Douglas C
  • Franco, Zulmarie
  • Sukumar, Madhusudhanan
  • Roychoudhuri, Rahul
  • Clever, David
  • Klebanoff, Christopher A
  • Surh, Charles D
  • Waldmann, Thomas A
  • Restifo, Nicholas P
  • Gattinoni, Luca
subjects:
  • Adoptive Immunotherapy
  • Homeostatic Cytokines
  • Lymphodepletion
  • Microrna-155
  • Cd8-Positive T-Lymphocytes -- Immunology
  • Cytokines -- Immunology
  • Micrornas -- Genetics
ispartof: Proceedings of the National Academy of Sciences of the United States of America, 13 January 2015, Vol.112(2), pp.476-81
description: Lymphodepleting regimens are used before adoptive immunotherapy to augment the antitumor efficacy of transferred T cells by removing endogenous homeostatic "cytokine sinks." These conditioning modalities, however, are often associated with severe toxicities. We found that microRNA-155 (miR-155) enabled tumor-specific CD8(+) T cells to mediate profound antitumor responses in lymphoreplete hosts that were not potentiated by immune-ablation. miR-155 enhanced T-cell responsiveness to limited amounts of homeostatic γc cytokines, resulting in delayed cellular contraction and sustained cytokine production. miR-155 restrained the expression of the inositol 5-phosphatase Ship1, an inhibitor of the serine-threonine protein kinase Akt, and multiple negative regulators of signal transducer and activator of transcription 5 (Stat5), including suppressor of cytokine signaling 1 (Socs1) and the protein tyrosine phosphatase Ptpn2. Expression of constitutively active Stat5a recapitulated the survival advantages...
language: eng
source:
identifier: E-ISSN: 1091-6490 ; PMID: 25548153 Version:1 ; DOI: 10.1073/pnas.1422916112
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titlemiR-155 augments CD8+ T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γc cytokines
creatorJi, Yun ; Wrzesinski, Claudia ; Yu, Zhiya ; Hu, Jinhui ; Gautam, Sanjivan ; Hawk, Nga V ; Telford, William G ; Palmer, Douglas C ; Franco, Zulmarie ; Sukumar, Madhusudhanan ; Roychoudhuri, Rahul ; Clever, David ; Klebanoff, Christopher A ; Surh, Charles D ; Waldmann, Thomas A ; Restifo, Nicholas P ; Gattinoni, Luca
ispartofProceedings of the National Academy of Sciences of the United States of America, 13 January 2015, Vol.112(2), pp.476-81
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subjectAdoptive Immunotherapy ; Homeostatic Cytokines ; Lymphodepletion ; Microrna-155 ; Cd8-Positive T-Lymphocytes -- Immunology ; Cytokines -- Immunology ; Micrornas -- Genetics
descriptionLymphodepleting regimens are used before adoptive immunotherapy to augment the antitumor efficacy of transferred T cells by removing endogenous homeostatic "cytokine sinks." These conditioning modalities, however, are often associated with severe toxicities. We found that microRNA-155 (miR-155) enabled tumor-specific CD8(+) T cells to mediate profound antitumor responses in lymphoreplete hosts that were not potentiated by immune-ablation. miR-155 enhanced T-cell responsiveness to limited amounts of homeostatic γc cytokines, resulting in delayed cellular contraction and sustained cytokine production. miR-155 restrained the expression of the inositol 5-phosphatase Ship1, an inhibitor of the serine-threonine protein kinase Akt, and multiple negative regulators of signal transducer and activator of transcription 5 (Stat5), including suppressor of cytokine signaling 1 (Socs1) and the protein tyrosine phosphatase Ptpn2. Expression of constitutively active Stat5a recapitulated the survival advantages...
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titlemiR-155 augments CD8+ T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γc cytokines
descriptionLymphodepleting regimens are used before adoptive immunotherapy to augment the antitumor efficacy of transferred T cells by removing endogenous homeostatic "cytokine sinks." These conditioning modalities, however, are often associated with severe toxicities. We found that microRNA-155 (miR-155) enabled tumor-specific CD8(+) T cells to mediate profound antitumor responses in lymphoreplete hosts that were not potentiated by immune-ablation. miR-155 enhanced T-cell responsiveness to limited amounts of homeostatic γc cytokines, resulting in delayed cellular contraction and sustained cytokine production. miR-155 restrained the expression of the inositol 5-phosphatase Ship1, an inhibitor of the serine-threonine protein kinase Akt, and multiple negative regulators of signal transducer and activator of transcription 5 (Stat5), including suppressor of cytokine signaling 1 (Socs1) and the protein tyrosine phosphatase Ptpn2. Expression of constitutively active Stat5a recapitulated the survival advantages...
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abstractLymphodepleting regimens are used before adoptive immunotherapy to augment the antitumor efficacy of transferred T cells by removing endogenous homeostatic "cytokine sinks." These conditioning modalities, however, are often associated with severe toxicities. We found that microRNA-155 (miR-155) enabled tumor-specific CD8(+) T cells to mediate profound antitumor responses in lymphoreplete hosts that were not potentiated by immune-ablation. miR-155 enhanced T-cell responsiveness to limited amounts of homeostatic γc cytokines, resulting in delayed cellular contraction and sustained cytokine production. miR-155 restrained the expression of the inositol 5-phosphatase Ship1, an inhibitor of the serine-threonine protein kinase Akt, and multiple negative regulators of signal transducer and activator of transcription 5 (Stat5), including suppressor of cytokine signaling 1 (Socs1) and the protein tyrosine phosphatase Ptpn2. Expression of constitutively active Stat5a recapitulated the survival advantages...
doi10.1073/pnas.1422916112
pmid25548153
date2015-01-13