title: Effector T cell subclasses associate with tumor burden in neurofibromatosis type 1 patients.
abstract: Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome caused by mutations of the NF1 gene and resulting dysregulation of the Ras-pathway. In addition to peripheral nerve tumors, affected tissues include the musculoskeletal and cardiovascular system. The immune system has recently been suggested as a possible modulator NF1-related phenotypes. Therefore, we determined the immune phenotype in NF1 patients and investigated its relationship with the phenotypic severity of NF1-related tumor manifestations. We quantified global leukocytes and lymphocyte subpopulations of peripheral blood from 37 NF1 patients and 21 healthy controls by flow cytometry. To associate immune phenotype with tumor phenotype, all NF1 patients underwent whole-body magnetic resonance imaging and total internal tumor volume was calculated. The immunophenotypes were compared among four NF1 groups with different total internal tumor burdens and between NF1 patients and non-NF1 subjects. We found that NF1 patients show a generalized lymphopenia. Closer analysis revealed that the CD8(+)/CD27(-) and CD8(+)/CD57(+) effector T cell fractions strongly increase in NF1 patients with low tumor load and decrease to levels below control in patients with high tumor load. Moreover, increased production of IL2, IFN-γ and TNF-α was found in T cells of NF1 patients upon phorbol-12-myristate acetate (PMA) stimulation compared to healthy controls. The data indicate that decreasing CD8(+)/CD57(+) and CD27(-) T cell fractions correspond to increasing tumor load in NF1 patients, potentially making these populations useful marker for internal tumor burden.
authors.affiliation: Neurologische Klinik, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Said
authors.initials: S
authors.lastname: Farschtschi
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Institute for Clinical Immunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Sawitzki
authors.affiliation: Neurologische Klinik, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.|College of Veterinary Medicine, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul, 151-742, Republic of Korea.
authors.forename: Su-Jun
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: Neurologische Klinik, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Lan
authors.initials: L
authors.lastname: Kluwe
authors.affiliation: Neurologische Klinik, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Victor F
authors.initials: VF
authors.lastname: Mautner
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. andreas.kurtz@charite.de.|College of Veterinary Medicine, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul, 151-742, Republic of Korea. andreas.kurtz@charite.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kurtz
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000145:classification* / Q000276:immunology* / Q000473:pathology; D047368:Tumor Burden; D055815:Young Adult
keywords: Immune phenotype; Neurofibromatosis type 1; Plexiform neurofibroma; T cell; Whole-body MRI