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Role of regulatory T cells in acute myeloid leukemia patients undergoing relapse-preventive immunotherapy

Artikel i vetenskaplig tidskrift
Författare Frida Ewald Sander
Stathis Kotsakis
Anna Rydström
Johan Aurelius
Rebecca E Riise
Charlotta Movitz
Elin Bernson
Roberta Kiffin
Anders Ståhlberg
Mats Brune
R. Foa
Kristoffer Hellstrand
Fredrik Bergh Thorén
Anna Martner
Publicerad i Cancer Immunology Immunotherapy
Volym 66
Nummer/häfte 11
Sidor 1473-1484
ISSN 0340-7004
Publiceringsår 2017
Publicerad vid Sahlgrenska Cancer Center
Institutionen för biomedicin, avdelningen för patologi
Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
Sidor 1473-1484
Språk en
Länkar https://doi.org/10.1007/s00262-017-...
Ämnesord Acute myeloid leukemia, Regulatory T cells, IL-2, Immunotherapy, 1st complete remission, reactive oxygen metabolites, recombinant, interleukin-2, nk cells, histaminergic regulation, myelogenous leukemia, phase-3 trial, expression, il-2, transplantation, Oncology, Immunology
Ämneskategorier Immunologi inom det medicinska området, Cancer och onkologi

Sammanfattning

Regulatory T cells - (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re: Mission Trial, NCT01347996, http://www.clinicaltrials.gov) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3(+)CD25(high)CD4(+) T-regs during immunotherapy and to determine the potential impact of T-regs on relapse risk and survival. We observed a pronounced increase in T-reg counts in peripheral blood during initial cycles of HDC/IL-2. The accumulating T-regs resembled thymic-derived natural T-regs (nT(regs)), showed augmented expression of CTLA-4 and suppressed the cell cycle proliferation of conventional T cells ex vivo. Relapse of AML was not prognosticated by T-reg counts at onset of treatment or after the first cycle of immunotherapy. However, the magnitude of T-reg induction was diminished in subsequent treatment cycles. Exploratory analyses implied that a reduced expansion of T-regs in later treatment cycles and a short T-reg telomere length were significantly associated with a favorable clinical outcome. Our results suggest that immunotherapy with HDC/IL-2 in AML entails induction of immunosuppressive T-regs that may be targeted for improved anti-leukemic efficiency.

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