Elevated CD3+ and CD8+ tumor-infiltrating immune cells correlate with prolonged survival in glioblastoma patients despite integrated immunosuppressive mechanisms in the tumor microenvironment and at the systemic level
We characterized GBM patients' tumor and systemic immune contexture with aim to reveal the mechanisms of immunological escape, their impact on patient outcome, and identify targets for immunotherapy. Increased CD3 T-cell infiltration was associated with prolonged survival independent of age, MGMT promoter methylation and post-operative treatment that implies potential for immunotherapy for GBM. Several mechanisms of escape were identified: within the tumor microenvironment: induced cD8+cD28 Foxp3 Tre that may tolerize antigen presenting cells, elevated CD73 and CD39 ectonucleotidases that suppress T-cell function, and at the systemic level: elevated IL-10 levels in serum, diminished helper T-cell counts, and upregulated inhibitory CTLA-4. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved.
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Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Tech Univ Munich, Inst Microbiol, Trogerstr 32, D-81675 Munich, GermanyFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Bauer, Stefan
Groh, Veronika
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Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Groh, Veronika
Wu, Jun
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DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Wu, Jun
Steinle, Alexander
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Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Steinle, Alexander
Phillips, Joseph H.
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DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Phillips, Joseph H.
Lanier, Lewis L.
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DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Lanier, Lewis L.
Spies, Thomas
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Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
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Univ Oxford, John Radcliffe Hosp, MRC Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DU, EnglandUniv Oxford, John Radcliffe Hosp, MRC Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DU, England
Chui, Cecilia S. C.
Li, Demin
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Univ Oxford, John Radcliffe Hosp, MRC Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DU, EnglandUniv Oxford, John Radcliffe Hosp, MRC Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DU, England
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Tech Univ Munich, Inst Microbiol, Trogerstr 32, D-81675 Munich, GermanyFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Bauer, Stefan
Groh, Veronika
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Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Groh, Veronika
Wu, Jun
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DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Wu, Jun
Steinle, Alexander
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Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Steinle, Alexander
Phillips, Joseph H.
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DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Phillips, Joseph H.
Lanier, Lewis L.
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DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Lanier, Lewis L.
Spies, Thomas
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Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
机构:
Univ Oxford, John Radcliffe Hosp, MRC Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DU, EnglandUniv Oxford, John Radcliffe Hosp, MRC Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DU, England
Chui, Cecilia S. C.
Li, Demin
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Univ Oxford, John Radcliffe Hosp, MRC Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DU, EnglandUniv Oxford, John Radcliffe Hosp, MRC Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DU, England