title: Frequency of telomerase-specific CD8+ T lymphocytes in patients with cancer.
abstract: Telomerase is considered a universal tumor-associated antigen (TAA) due to its high rate of expression by cancers (approximately 90%), and clinical trials are in progress to test the immunotherapeutical efficacy of antitelomerase immunization in patients with cancer. However, the data concerning frequency and functional activity of telomerase-specific cytotoxic T lymphocytes (CTLs) in patients with cancer are few and conflicting, although their knowledge would be mandatory to predict the efficacy of telomerase-specific immunotherapy in selected patients. We performed this study to analyze frequency and cytolytic function of circulating CD8+ T lymphocytes specific for the p540 telomerase peptide in a series of human leukocyte antigen (HLA)-A2+ cancer patients. The results show that most patients with cancer have circulating telomerase-specific CD8+ T lymphocytes, but a high frequency of telomerase-specific CTLs are present only in a fraction of them. Furthermore, CTL lines able to kill telomerase-positive tumor cells, including autologous cancer cells, can be expanded ex vivo from some, but not all, patients with cancer. In conclusion, the results of the study support the development of clinical protocols using telomerase peptides as an immunizing agent. However, they underline the necessity to study single patients immunologically before undergoing vaccination, to select the patients adequately, and to eventually adapt the immunization schedule to the patient's immunologic status.
authors.affiliation: Department of Internal Medicine and Center of Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto XV no. 6, 16132 Genova, Italy. gfilaci@unige.it
authors.forename: Gilberto
authors.initials: G
authors.lastname: Filaci
authors.forename: Marco
authors.initials: M
authors.lastname: Fravega
authors.forename: Maurizio
authors.initials: M
authors.lastname: Setti
authors.forename: Paolo
authors.initials: P
authors.lastname: Traverso
authors.forename: Enrico
authors.initials: E
authors.lastname: Millo
authors.forename: Daniela
authors.initials: D
authors.lastname: Fenoglio
authors.forename: Simone
authors.initials: S
authors.lastname: Negrini
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrera
authors.forename: Andrea
authors.initials: A
authors.lastname: Romagnoli
authors.forename: Monica
authors.initials: M
authors.lastname: Basso
authors.forename: Paola
authors.initials: P
authors.lastname: Contini
authors.forename: Marta
authors.initials: M
authors.lastname: Rizzi
authors.forename: Massimo
authors.initials: M
authors.lastname: Ghio
authors.forename: Umberto
authors.initials: U
authors.lastname: Benatti
authors.forename: Gianluca
authors.initials: G
authors.lastname: Damonte
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Ravetti
authors.forename: Giorgio
authors.initials: G
authors.lastname: Carmignani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zanetti
authors.forename: Francesco
authors.initials: F
authors.lastname: Indiveri
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology*; D045744:Cell Line, Tumor; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008212:Lymphocyte Depletion; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology; D019098:Telomerase / Q000097:blood*
chemical_list: D015789:HLA-A2 Antigen; D019098:Telomerase