title: Nucleophosmin is recognized by a cytotoxic T cell line derived from a rectal carcinoma patient.
abstract: Immunotherapy of colorectal carcinoma (CRC) has great promise as the presence of T lymphocytes in CRC tissues in situ is correlated with reduced recurrence and increased survival. Thus, identification of the antigens recognized by T cells of CRC patients may permit development of vaccines with potential benefit for these patients. Using expression cloning, we identified the antigen, nucleophosmin (Npm), recognized by an HLA-A1 restricted cytotoxic T lymphocyte (CTL) line derived from the peripheral blood mononuclear cells (PBMC) of a rectal cancer patient. A decamer peptide derived from the Npm sequence sensitized peptide-pulsed HLA-A1 positive cells to lysis by the CTL line. The peptide also induced proliferative and cytotoxic T lymphocytes in the PBMC of 4 of 6 CRC patients, which lysed HLA-A1 positive peptide-pulsed target cells and CRC cells endogenously expressing Npm. Overexpression of Npm by tumors of various histological types, recognition of the antigen by T cells derived from different CRC patients and association of the antigen with poor prognostic outcome make it a promising target for immunotherapeutic intervention in cancer patients.
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia PA 19104, USA.
authors.forename: Rolf K
authors.initials: RK
authors.lastname: Swoboda
authors.forename: Rajasekharan
authors.initials: R
authors.lastname: Somasundaram
authors.forename: Laura
authors.initials: L
authors.lastname: Caputo
authors.forename: Klara
authors.initials: K
authors.lastname: Berencsi
authors.forename: Paul
authors.initials: P
authors.lastname: von Franzke
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Taylor
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Meropol
authors.forename: Elin
authors.initials: E
authors.lastname: Sigurdson
authors.forename: Eric
authors.initials: E
authors.lastname: Miller
authors.forename: Dorothee
authors.initials: D
authors.lastname: Herlyn
mesh_terms: D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology; D005260:Female; D015788:HLA-A1 Antigen / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology / Q000473:pathology; D009687:Nuclear Proteins / Q000276:immunology*; D000090243:Nucleophosmin; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D012004:Rectal Neoplasms / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D015788:HLA-A1 Antigen; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D010446:Peptide Fragments; D000090243:Nucleophosmin