title: Long-term survival in multiple myeloma is associated with a distinct immunological profile, which includes proliferative cytotoxic T-cell clones and a favourable Treg/Th17 balance.
abstract: Despite improved outcomes in multiple myeloma (MM), a cure remains elusive. However, even before the current therapeutic era, 5% of patients survived >10 years and we propose that immune factors contribute to this longer survival. We identified patients attending our clinic, who had survived >10 years (n=20) and analysed their blood for the presence of T-cell clones, T-regulatory cells (Tregs) and T helper 17 (Th17) cells. These results were compared with MM patients with shorter follow-up and age-matched healthy control donors. The frequency of cytotoxic T-cell clonal expansions in patients with <10 years follow-up (MM patients) was 54% (n=144), whereas it was 100% (n=19/19) in the long-survivors (LTS-MM). T-cell clones from MM patients proliferated poorly in vitro, whereas those from LTS-MM patients proliferated readily (median proliferations 6.1% and 61.5%, respectively (P<0.0001)). In addition, we found significantly higher Th17 cells and lower Tregs in the LTS-MM group when compared with the MM group. These results indicate that long-term survival in MM is associated with a distinct immunological profile, which is consistent with decreased immune suppression.
authors.affiliation: 1] Institute of Haematology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia [2] Dendritic Cell Biology and Therapeutics, ANZAC Research Institute, Concord Hospital, Sydney, New South Wales, Australia [3] Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: C
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authors.forename: H
authors.initials: H
authors.lastname: Suen
authors.forename: R
authors.initials: R
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Favaloro
authors.forename: E
authors.initials: E
authors.lastname: Aklilu
authors.forename: J
authors.initials: J
authors.lastname: Gibson
authors.forename: P J
authors.initials: PJ
authors.lastname: Ho
authors.forename: H
authors.initials: H
authors.lastname: Iland
authors.forename: P
authors.initials: P
authors.lastname: Fromm
authors.forename: N
authors.initials: N
authors.lastname: Woodland
authors.forename: N
authors.initials: N
authors.lastname: Nassif
authors.forename: D
authors.initials: D
authors.lastname: Hart
authors.forename: D E
authors.initials: DE
authors.lastname: Joshua
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