Role of regulatory T cells in acute myeloid leukemia patients undergoing relapse-preventive immunotherapy (original) (raw)
2017, Cancer Immunology, Immunotherapy
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. Keywords Acute myeloid leukemia • Regulatory T cells • IL-2 • Immunotherapy Abbreviations Allo-SCT Allogeneic stem cell transplant AML Acute myeloid leukemia C1D1 Cycle 1, day 1 C1D21 Cycle 1, day 21 C3D1 Cycle 3, day 1 C3D21 Cycle 3, day 21 CR Complete remission GvHD Graft-versus-host disease HDC Histamine dihydrochloride iT regs Induced regulatory T cells LFS Leukemia-free survival NOX2 Nicotinamide adenine dinucleotide phosphate oxidase isoform 2 nT regs Natural regulatory T cells OS Overall survival qPCR Quantitative PCR ROS Reactive oxygen species T cons Conventional T cells Abstract Regulatory T cells (T regs) 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 postconsolidation 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 Electronic supplementary material The online version of this article (
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