title: Viral antigen-specific CD8+ T-cell responses are impaired in multiple myeloma.
abstract: Multiple myeloma (MM) is associated with defects of humoral and cellular immunity, however, little is known about the frequency and function of antigen-specific CD8+ T cells. Such information might be critical for the development of immunotherapy for MM patients. As a model, we assessed the frequency and proliferation of CD8+ T cells specific for HLA-A*0201-restricted immunodominant epitopes from influenza A (Inf A) and Epstein-Barr virus (EBV). Experiments in identical twins demonstrated reduced numbers of antigen-specific T cells after ex-vivo antigenic challenge in the MM twin when compared with the healthy twin. Similarly, the proliferation and frequency of EBV- and Inf A-specific T cells was also significantly reduced in a cohort of 24 previously untreated or conventionally treated MM patients when compared with 19 healthy individuals. In contrast, MM patients studied after receiving an autologous stem cell transplantation showed strikingly higher frequencies of EBV-specific T cells with potential to proliferate ex vivo, suggesting that EBV-specific T cells are readily expandable under these circumstances. These data identify an impaired response of CD8+ T cells in MM patients, which might in part explain the relatively limited success of anti-MM immunisations. Prospective studies will determine whether such immune assessment strategies may identify patients more likely to benefit from cancer immunotherapy.
authors.affiliation: Department of Adult Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: Britta
authors.initials: B
authors.lastname: Maecker
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.forename: Michael S
authors.initials: MS
authors.lastname: von Bergwelt-Baildon
authors.forename: Edie
authors.initials: E
authors.lastname: Weller
authors.forename: Robert H
authors.initials: RH
authors.lastname: Vonderheide
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Robert L
authors.initials: RL
authors.lastname: Schlossman
authors.forename: Isaura A
authors.initials: IA
authors.lastname: Menezes
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Xia
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Lee M
authors.initials: LM
authors.lastname: Nadler
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000956:Antigens, Viral / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D002472:Cell Transformation, Viral; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes; D009980:Influenza A virus / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D016827:CD8 Antigens; D016056:Immunodominant Epitopes