title: In vitro quantification of the cytotoxic T lymphocyte response against human telomerase reverse transcriptase in breast cancer.
abstract: Telomerase is expressed in approximately 90% of breast cancers but not in normal somatic cells. The catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), is a widely expressed tumour-associated antigen against which specific cytotoxic T lymphocyte (CTL) responses have been identified. Human CD8+ CTL have been shown to recognise hTERT synthetic peptides in an HLA-restricted manner and to lyse hTERT+ tumour cells. This study has investigated the specific CD8+ CTL response in a defined cohort of primary breast cancer patients against 3 hTERT peptides using an IFNgamma ELISpot assay. A specific CD8+ CTL response against at least one of the hTERT peptides was observed in 75% of cancer patients, with 8/17 patients responding to both HLA-A2 restricted peptides. In contrast, 38% of normal healthy female controls responded against a single peptide only. This suggests that a specific immune response exists against hTERT in breast cancer patients and that hTERT is a suitable target for tumour-based immunotherapy.
authors.affiliation: Department of Surgery, Postgraduate Medical Institute, University of Hull, Hull, UK.
authors.forename: Shoba Maria Prescilla
authors.initials: SM
authors.lastname: Amarnath
authors.forename: Charlotte Emma
authors.initials: CE
authors.lastname: Dyer
authors.forename: Aswatha
authors.initials: A
authors.lastname: Ramesh
authors.forename: Obi
authors.initials: O
authors.lastname: Iwuagwu
authors.forename: Philip John
authors.initials: PJ
authors.lastname: Drew
authors.forename: John
authors.initials: J
authors.lastname: Greenman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001940:Breast / Q000276:immunology / Q000502:physiology; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004268:DNA-Binding Proteins; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000276:immunology*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019098:Telomerase / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; D010446:Peptide Fragments; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D019098:Telomerase