Detection and preliminary characterization of CD8+ T lymphocytes specific for Wilms’ tumor antigen in patients with non-Hodgkin lymphoma

摘要

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 NHL patients. Utilizing a WT1 overlapping peptide library, we discovered that a large percentage of NHL patients 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 they were cytotoxic to WT1 peptide library-loaded T2 cells and WT1 antigen-primed autologous EBV-transformed B cell lines (EBV-LCL) and expressed interferon gamma (IFN-γ). In addition, we detected WT1 mRNA transcripts in diseased lymph node tissues of NHL patients utilizing real-time quantitative polymerase chain reaction (RT-qPCR) technology. These results are the first example of strong T cell reactivity against WT1 in NHL patients 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.