期刊
CLINICAL IMMUNOLOGY
卷 129, 期 2, 页码 230-240出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2008.07.024
关键词
HLA-multimers; Spontaneously occurring CD8(+) T-cell responses; Peptide-specific CD8(+) T cells; Survivin; Survivin-2B
类别
资金
- European Union-European Social Fund
- Greek Ministry of Development-GSRT [04EP09]
- National Resources-EPEAEK II (Pythagoras)
- Marie Curie Incoming International Fellowship [MIF1-CT-2006-021795]
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 mate 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. (C) 2008 Elsevier Inc. All rights reserved.
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