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

Autor: Johan Aurelius, Rebecca E. Riise, Charlotta Movitz, Roberta Kiffin, Kristoffer Hellstrand, Elin Bernson, Frida Ewald Sander, Fredrik B. Thorén, Anna Rydström, Malin S Nilsson, Anna Martner, Anders Ståhlberg, Robin Foà, Mats Brune
Rok vydání: 2017
Předmět:
Myeloid
Male
0301 basic medicine
Cancer Research
T-Lymphocytes
medicine.medical_treatment
T-Lymphocytes
Regulatory
0302 clinical medicine
Outcome Assessment
Health Care
Immunology and Allergy
Leukemia
Remission Induction
Myeloid leukemia
FOXP3
Forkhead Transcription Factors
hemic and immune systems
Regulatory T cells
Middle Aged
Telomere
Cell cycle
Prognosis
Regulatory
Local
Oncology
Leukemia
Myeloid
030220 oncology & carcinogenesis
Acute Disease
Original Article
Female
Immunotherapy
Histamine
Adult
Adolescent
Immunology
chemical and pharmacologic phenomena
Outcome Assessment (Health Care)
Young Adult
03 medical and health sciences
Immune system
medicine
Humans
Aged
Proportional Hazards Models
Acute myeloid leukemia
business.industry
IL-2
Interleukin-2 Receptor alpha Subunit
Cancer
medicine.disease
Neoplasm Recurrence
030104 developmental biology
Interleukin-2
Multivariate Analysis
Neoplasm Recurrence
Local
business
Ex vivo
Zdroj: Cancer Immunology, Immunotherapy
ISSN: 1432-0851
0340-7004
Popis: 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. Electronic supplementary material The online version of this article (doi:10.1007/s00262-017-2040-9) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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