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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

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

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