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

被引:310
作者
Kmiecik, Justyna [1 ]
Poli, Aurelie [1 ]
Brons, Nicolaas H. C.
Waha, Andreas [2 ]
Eide, Geir Egil [3 ,4 ]
Enger, Per Oyvind [5 ]
Zimmer, Jacques
Chekenya, Martha [1 ,6 ]
机构
[1] Univ Bergen, Dept Biomed, N-5009 Bergen, Norway
[2] Univ Hosp, Dept Neuropathol, Bonn, Germany
[3] Haukeland Hosp, Clin Res Ctr, N-5021 Bergen, Norway
[4] Univ Bergen, Dept Global Publ Hlth & Primary Care, N-5020 Bergen, Norway
[5] Haukeland Hosp, Dept Neurosurg, N-5021 Bergen, Norway
[6] Univ Bergen, Dept Clin Dent, N-5009 Bergen, Norway
关键词
GBM; Tumor infiltrating cells; Regulatory T cells; Antigen presenting cells; REGULATORY T-CELLS; MGMT PROMOTER METHYLATION; NATURAL-KILLER-CELLS; NK CELLS; ADJUVANT TEMOZOLOMIDE; PROGNOSTIC VALUE; RECEPTOR; CANCER; EXPRESSION; NKG2D;
D O I
10.1016/j.jneuroim.2013.08.013
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:71 / 83
页数:13
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