1. Cytolytic T-cell response to the PASD1 cancer testis antigen in patients with diffuse large B-cell lymphoma.
- Author
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Ait-Tahar, Kamel, Liggins, Amanda P., Collins, Graham P., Campbell, Andrew, Barnardo, Martin, Lawrie, Charles, Moir, Donald, Hatton, Chris, Banham, Alison H., and Pulford, Karen
- Subjects
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ADULT T-cell leukemia , *ANTIGENS , *IMMUNOTHERAPY , *LYMPHOMAS , *CELL-mediated cytotoxicity - Abstract
The identification of immunogenic cancer testis antigens (CTAs) as immunotherapeutic targets represents one approach to improve treatment options for diffuse large B-cell lymphoma (DLBCL). We previously identified PASD1 [PAS (Per ARNT Sim) domain containing 1 (PASD1)], a DLBCL-associated CTA that was expressed in a range of hematopoietic malignancies. The aim of the present study was to investigate the presence of a cytotoxic T-cell (CTL) response to PASD1 in DLBCL patients. A significant γ-interferon (IFN) release was detected in 21/29 HLA-A*0201-positive DLBCL patients (18 de novo DLBCL, two transformed DLBCL and one T-cell rich B-cell lymphoma) following short-term culture of their peripheral blood mononuclear cells stimulated with five HLA-A*0201-restricted PASD1 peptides. No significant responses were detected in 21 HLA-A*0201-negative DLBCL patients (12 de novo DLBCL, seven transformed DLBCL, two T-cell rich B-cell lymphoma) or six normal subjects. CTL cell lines were able to lyse PASD1-positive tumour cells in a major histocompatibility complex-Class I dependent manner. The presence of a γ-IFN response correlated with PASD1 protein expression in the tumour cells in 12/15 cases studied. This is the first report of a CTL response to a CTA in DLBCL. Our results provide additional valuable evidence supporting PASD1 as a potential immunotherapeutic target for the treatment of DLBCL and other malignancies. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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