Cytolytic T-cell response to the PASD1 cancer testis antigen in patients with diffuse large B-cell lymphoma

Br J Haematol. 2009 Aug;146(4):396-407. doi: 10.1111/j.1365-2141.2009.07761.x. Epub 2009 Jun 22.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antigens, Neoplasm
  • Antigens, Nuclear
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Histocompatibility Antigens Class I
  • PASD1 protein, human
  • Interferon-gamma