TY - JOUR
T1 - Viral antigen-specific CD8+ T-cell responses are impaired in multiple myeloma
AU - Maecker, Britta
AU - Anderson, Karen S.
AU - Von Bergwelt-Baildon, Michael S.
AU - Weller, Edie
AU - Vonderheide, Robert H.
AU - Richardson, Paul G.
AU - Schlossman, Robert L.
AU - Menezes, Isaura A.
AU - Xia, Zhinan
AU - Munshi, Nikhil C.
AU - Anderson, Kenneth C.
AU - Nadler, Lee M.
AU - Schultze, Joachim L.
PY - 2003/6
Y1 - 2003/6
N2 - 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.
AB - 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.
KW - Multiple myeloma
KW - T cells
KW - Tetramer
UR - http://www.scopus.com/inward/record.url?scp=0038268128&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038268128&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2141.2003.04375.x
DO - 10.1046/j.1365-2141.2003.04375.x
M3 - Article
C2 - 12786794
AN - SCOPUS:0038268128
SN - 0007-1048
VL - 121
SP - 842
EP - 848
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 6
ER -