title: Detection and preliminary characterization of CD8+T lymphocytes specific for Wilms' tumor antigen in patients with non-Hodgkin lymphoma.
abstract: Wilms' tumor antigen (WT1) is overexpressed in many different solid tumors and hematologic malignancies. However, little is known about WT1 expression or WT1-specific immune responses in patients with non-Hodgkin lymphoma (NHL). In a cross-sectional survey study, we investigated the immune recognition of WT1 by patients with NHL. Utilizing a WT1 overlapping peptide library, we discovered that a large percentage of patients with NHL of all grades maintain WT1-specific T cells. Ex vivo frequencies of these T cells measured from unfractionated samples by the CD137 activation marker assay were high in many patients (some > 1% CD8+). Using standard in vitro techniques we discovered that they were cytotoxic to WT1 peptide library-loaded T2 cells and WT1 antigen-primed autologous Epstein-Barr virus-transformed B cell lines (EBV-LCLs) and expressed interferon gamma (IFN-γ). In addition, we detected WT1 mRNA transcripts in diseased lymph node tissues of patients with NHL utilizing real-time quantitative polymerase chain reaction (RT-qPCR) technology. These results are the first example of strong T cell reactivity against WT1 in patients with NHL which also demonstrate strong cytotoxicity against peptide-loaded tumor cells. The potential for developing WT1 as a target for immunotherapy in NHL deserves further exploration.
authors.affiliation: Division of Translational Vaccine Research.
authors.forename: Anna
authors.initials: A
authors.lastname: Israyelyan
authors.forename: Corinna
authors.initials: C
authors.lastname: La Rosa
authors.forename: Weimin
authors.initials: W
authors.lastname: Tsai
authors.forename: Teodora
authors.initials: T
authors.lastname: Kaltcheva
authors.forename: Tumul
authors.initials: T
authors.lastname: Srivastava
authors.forename: Lia
authors.initials: L
authors.lastname: Aquino
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Li
authors.forename: Young
authors.initials: Y
authors.lastname: Kim
authors.forename: Joycelynne
authors.initials: J
authors.lastname: Palmer
authors.forename: Leanne
authors.initials: L
authors.lastname: Streja
authors.forename: David
authors.initials: D
authors.lastname: Senitzer
authors.forename: John A
authors.initials: JA
authors.lastname: Zaia
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Nakamura
authors.forename: Don J
authors.initials: DJ
authors.lastname: Diamond
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010455:Peptides / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism; D025721:WT1 Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D025721:WT1 Proteins; D007371:Interferon-gamma