title: Association of antigen-specific T-cell responses with antigen expression and immunoparalysis in multiple myeloma.
abstract: OBJECTIVE
  Cancer testis antigens (CTA) are immunotherapeutical targets aberrantly expressed on multiple myeloma cells, especially at later stages, when a concomitant immunoparesis hampers vaccination approaches.
  
  
  METHODS
  We assessed the expression of the multiple myeloma antigen HM1.24 (reported present in all malignant plasma cells) and the CTAs MAGE-A2/A3 and NY-ESO-1 (aberrantly expressed in a subset of patients with myeloma), in CD138-purified myeloma cells by qRT-PCR (n = 149). In a next step, we analyzed the antigen-specific T-cell responses against these antigens by IFNγ EliSpot assay (n = 145) and granzymeB ELISA (n = 62) in relation to stage (tumor load) and expression of the respective antigen.
  
  
  RESULTS
  HM1.24 is expressed in all plasma-cell samples, whereas CTAs are significantly more frequent in later stages. HM1.24-specific T-cell responses, representing the immunologic status, significantly decreased from healthy donors to advanced disease. For the CTAs, the probability of T-cell responses increased in early and advanced stages compared with healthy donors, paralleling increased probability of expression. In advanced stages, T-cell responses decreased because of immunoparesis.
  
  
  CONCLUSIONS
  In conclusion, specific T-cell responses in myeloma are triggered by antigen expression but suppressed by tumor load. Future CTA-based immunotherapeutical approaches might target early plasma-cell diseases to establish prophylactically a specific T-cell response against late-stage antigens in immunocompetent patients.
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Fichtner
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany. National Center for Tumor Diseases Heidelberg, University of Heidelberg, Heidelberg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Engelhardt
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Meißner
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Neuber
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Fatime
authors.initials: F
authors.lastname: Krasniqi
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Raab
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schönland
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany. National Center for Tumor Diseases Heidelberg, University of Heidelberg, Heidelberg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany. michael.hundemer@med.uni-heidelberg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Hundemer
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D009101:Multiple Myeloma / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000951:Antigens, Neoplasm