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

J Neuroimmunol. 2013 Nov 15;264(1-2):71-83. doi: 10.1016/j.jneuroim.2013.08.013. Epub 2013 Aug 31.


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(+) Tregs 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.

Keywords: Antigen presenting cells; GBM; Regulatory T cells; Tumor infiltrating cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism
  • Brain Neoplasms / immunology*
  • Brain Neoplasms / mortality
  • CD28 Antigens / metabolism*
  • CD3 Complex / metabolism*
  • CTLA-4 Antigen / metabolism
  • Child
  • Female
  • Follow-Up Studies
  • Forkhead Transcription Factors / metabolism
  • Glioblastoma / immunology*
  • Glioblastoma / mortality
  • Humans
  • Immunosuppressive Agents / immunology
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Macrophages / metabolism
  • Male
  • Microglia / metabolism
  • Middle Aged
  • Young Adult


  • Antigens, CD
  • CD28 Antigens
  • CD3 Complex
  • CTLA-4 Antigen
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Immunosuppressive Agents