title: Baseline levels of CD8+ T cells against survivin and survivin-2B in the blood of lung cancer patients and cancer-free individuals.
abstract: Survivin and its variant survivin-2B have been considered as potential candidates for cancer immunotherapy. The magnitude however of spontaneously occurring CD8(+) T cells circulating precursor CTLs (pCTL), has never been evaluated. We set out to measure in 20 patients with lung carcinomas and 5 aged matched healthy male individuals (expressing HLA-A2 and/or -A24), the frequency of pCTLs specific for two naturally processed and presented peptides of survivin (LTLGEFLKL presented by HLA-A2) and survivin-2B (AYACNTSTL presented by HLA-A24) since these peptides are the only ones used in immunotherapeutic trials. The frequency of peptide-specific pCTLs was estimated using a sensitive method that combines HLA-multimer flow cytometric technology with a previous step of in vitro amplification under limiting dilution conditions. Anti-survivin or anti-survivin-2B specific CTL clones were not detected in 17 out of the 21 tested patients, and in none of the healthy individuals. In a number of peripheral blood mononuclear cell microcultures of the remaining 4 patients, diffuse clusters stained weakly by the HLA-multimers were observed which were not amplified after further stimulation and, therefore, they were finally considered as negative. The significance of the levels of spontaneously occurring CTL-responses against survivin and survivin-2B peptides, in cancer patients and cancer-free subjects, remains to be elucidated and it would be interesting to be considered in relation to the clinical efficacy of anti-cancer vaccination protocols.
authors.affiliation: Cancer Immunology Unit, Department of Immunology and Histocompatibility, School of Medicine, University of Thessaly, University Hospital of Larissa, GR-411 10 Larissa, Greece. vkaran@med.uth.gr
authors.forename: Vaios
authors.initials: V
authors.lastname: Karanikas
authors.forename: Faye
authors.initials: F
authors.lastname: Soukou
authors.forename: Fani
authors.initials: F
authors.lastname: Kalala
authors.forename: Theodora
authors.initials: T
authors.lastname: Kerenidi
authors.forename: Evangelia S
authors.initials: ES
authors.lastname: Grammoustianou
authors.forename: Konstantinos I
authors.initials: KI
authors.lastname: Gourgoulianis
authors.forename: Anastasios E
authors.initials: AE
authors.lastname: Germenis
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007371:Interferon-gamma / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000276:immunology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000276:immunology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*; D016133:Polymerase Chain Reaction; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; C072013:MAGEA3 protein, human; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D007371:Interferon-gamma