Cytolytic T-cell response to the PASD1 cancer testis antigen in patients with diffuse large B-cell lymphoma.
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.
Ait-Tahar
Kamel
K
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Liggins
Amanda P
AP
Collins
Graham P
GP
Campbell
Andrew
A
Barnardo
Martin
M
Lawrie
Charles
C
Moir
Donald
D
Hatton
Chris
C
Banham
Alison H
AH
Pulford
Karen
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000627:therapeutic use*; D034961:Antigens, Nuclear / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D005260:Female; D005455:Fluorescent Antibody Technique; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D055815:Young Adult
D000951:Antigens, Neoplasm; D034961:Antigens, Nuclear; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; C515845:PASD1 protein, human; D007371:Interferon-gamma