title: Myeloma skews regulatory T and pro-inflammatory T helper 17 cell balance in favor of a suppressive state.
abstract: Abstract Discrepancies in the literature between regulatory T cell (Treg) and pro-inflammatory T helper 17 (Th17) numbers in multiple myeloma (MM) can be largely explained by technical differences in methodology and patient selection. In this study, Treg cells were defined as CD3(+)CD4(+)CD25(++)CD127(lo) cells. Patients with MM (n = 20) had a significant imbalance in Treg/Th17 ratio when compared with either aged-matched controls (n = 28) or other monoclonal gammopathies, and this was associated with a significantly worse survival. The percent Treg in bone marrow of patients with MM was higher than that in matched peripheral blood samples (p = 0.02), although FOXP3 expression within bone marrow T cells was lower (p = 0.02). We observed increased Treg function, both in vivo and in vitro, due at least partially to an increase in CTLA-4 expression by concurrent treatment with dexamethasone and immune modulatory compounds (iMiDs). We suggest that immunoregulatory balance is important during active chemotherapy and that conclusions related to the immunostimulatory effect of iMiDs based on in vitro testing must be considered with caution.
authors.affiliation: Institute of Haematology, Royal Prince Alfred Hospital , Sydney, NSW , Australia.
authors.forename: James
authors.initials: J
authors.lastname: Favaloro
authors.forename: Ross
authors.initials: R
authors.lastname: Brown
authors.forename: Esther
authors.initials: E
authors.lastname: Aklilu
authors.forename: Shihong
authors.initials: S
authors.lastname: Yang
authors.forename: Hayley
authors.initials: H
authors.lastname: Suen
authors.forename: Derek
authors.initials: D
authors.lastname: Hart
authors.forename: Phillip
authors.initials: P
authors.lastname: Fromm
authors.forename: John
authors.initials: J
authors.lastname: Gibson
authors.forename: Liane
authors.initials: L
authors.lastname: Khoo
authors.forename: P Joy
authors.initials: PJ
authors.lastname: Ho
authors.forename: Douglas
authors.initials: D
authors.lastname: Joshua
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D018655:Lymphocyte Count; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism; D010265:Paraproteinemias / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen