Detection and preliminary characterization of CD8+T lymphocytes specific for Wilms' tumor antigen in patients with non-Hodgkin lymphoma. Issue 11 (November 2013)

• Record Type: Journal Article
• Authors: Israyelyan, Anna; La Rosa, Corinna; Tsai, Weimin; Kaltcheva, Teodora; Srivastava, Tumul; Aquino, Lia; Li, Jianqiang; Kim, Young; Palmer, Joycelynne; Streja, Leanne; Senitzer, David; Zaia, John A.; Rosenwald, Andreas; Forman, Stephen J.; Nakamura, Ryotaro; Diamond, Don J.
• Is Part Of: Leukemia & lymphoma. Volume 54:Issue 11(2013:Nov.)
• Page Start: 2490
• Page End: 2499
• Publication Date: 2013-11
• Subjects: Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2013.783910
• Languages: English
• ISSNs: 1042-8194

Abstract

<abstract> <title>Abstract</title> <p>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. <italic>Ex vivo</italic> frequencies of these T cells measured from unfractionated samples by the CD137 activation marker assay were high in many patients (some &gt; 1% CD8+). Using standard <italic>in vitro</italic> 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.</p> </abstract>