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Cancer Immunol Immunother. 2017 Nov;66(11):1473-1484. doi: 10.1007/s00262-017-2040-9. Epub 2017 Jul 18.

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

Author information

1
TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Medicinaregatan 1F, Box 425, 413 90, Gothenburg, Sweden.
2
Department of Hematology, University of Gothenburg, 413 45, Gothenburg, Sweden.
3
Department of Pathology and Genetics, Sahlgrenska Cancer Center, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 1F, 413 90, Gothenburg, Sweden.
4
Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Via Benevento 6, 00161, Rome, Italy.
5
TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Medicinaregatan 1F, Box 425, 413 90, Gothenburg, Sweden. anna.martner@gu.se.

Abstract

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+CD25highCD4+ Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival. We observed a pronounced increase in Treg counts in peripheral blood during initial cycles of HDC/IL-2. The accumulating Tregs resembled thymic-derived natural Tregs (nTregs), 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 Treg counts at onset of treatment or after the first cycle of immunotherapy. However, the magnitude of Treg induction was diminished in subsequent treatment cycles. Exploratory analyses implied that a reduced expansion of Tregs in later treatment cycles and a short Treg 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 Tregs that may be targeted for improved anti-leukemic efficiency.

KEYWORDS:

Acute myeloid leukemia; IL-2; Immunotherapy; Regulatory T cells

PMID:
28721449
PMCID:
PMC5645432
DOI:
10.1007/s00262-017-2040-9
[Indexed for MEDLINE]
Free PMC Article

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