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.