Frequency of telomerase-specific CD8+ T lymphocytes in patients with cancer.
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.
Filaci
Gilberto
G
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
Fravega
Marco
M
Setti
Maurizio
M
Traverso
Paolo
P
Millo
Enrico
E
Fenoglio
Daniela
D
Negrini
Simone
S
Ferrera
Francesca
F
Romagnoli
Andrea
A
Basso
Monica
M
Contini
Paola
P
Rizzi
Marta
M
Ghio
Massimo
M
Benatti
Umberto
U
Damonte
Gianluca
G
Ravetti
Jean Louis
JL
Carmignani
Giorgio
G
Zanetti
Maurizio
M
Indiveri
Francesco
F
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*
D015789:HLA-A2 Antigen; D019098:Telomerase