title: 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.
abstract: 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.
authors.affiliation: Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.
authors.forename: Justyna
authors.initials: J
authors.lastname: Kmiecik
authors.forename: Aurélie
authors.initials: A
authors.lastname: Poli
authors.forename: Nicolaas H C
authors.initials: NH
authors.lastname: Brons
authors.forename: Andreas
authors.initials: A
authors.lastname: Waha
authors.forename: Geir Egil
authors.initials: GE
authors.lastname: Eide
authors.forename: Per Øyvind
authors.initials: PØ
authors.lastname: Enger
authors.forename: Jacques
authors.initials: J
authors.lastname: Zimmer
authors.forename: Martha
authors.initials: M
authors.lastname: Chekenya
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D001932:Brain Neoplasms / Q000276:immunology* / Q000401:mortality; D018106:CD28 Antigens / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism*; D060908:CTLA-4 Antigen / Q000378:metabolism; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005909:Glioblastoma / Q000276:immunology* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D018106:CD28 Antigens; D017252:CD3 Complex; D060908:CTLA-4 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents
keywords: Antigen presenting cells; GBM; Regulatory T cells; Tumor infiltrating cells