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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 gamma-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 gamma-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.

Original publication

DOI

10.1111/j.1365-2141.2009.07761.x

Type

Journal article

Journal

Br J Haematol

Publication Date

08/2009

Volume

146

Pages

396 - 407

Keywords

Adult, Aged, Aged, 80 and over, Antigen Presentation, Antigens, Neoplasm, Antigens, Nuclear, Cell Line, Tumor, Cytotoxicity Tests, Immunologic, Female, Fluorescent Antibody Technique, HLA-A Antigens, HLA-A2 Antigen, Histocompatibility Antigens Class I, Humans, Immunization, Interferon-gamma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Male, Middle Aged, T-Lymphocytes, T-Lymphocytes, Cytotoxic, Young Adult