Journal article
Expansion of Effector Memory Regulatory T Cells Represents a Novel Prognostic Factor in Lower Risk Myelodysplastic Syndrome
The Journal of immunology (1950), Vol.189(6), pp.3198-3208
09/15/2012
DOI: 10.4049/jimmunol.1200602
PMCID: PMC3436939
PMID: 22875800
Abstract
Myelodysplastic syndromes are premalignant diseases characterized by cytopenias, myeloid dysplasia, immune dysregulation with association to autoimmunity, and variable risk for acute myeloid leukemia transformation. Studies of FOXP3(+) regulatory T cells (Tregs) indicate that the number and/or activation state may influence cancer progression in these patients. Focusing on patients with a lower risk for leukemia transformation, 18 (34.6%) of 52 patients studied displayed an altered Treg compartment compared with age-matched controls. Delineation of unique Treg subsets revealed that an increase in the absolute number of CD4(+)FOXP3(+)CD25(+)CD127(low)CD45RA(-)CD27(-) Tregs (effector memory Tregs [Treg(EM)]) was significantly associated with anemia (p = 0.046), reduced hemoglobin (p = 0.038), and blast counts >= 5% (p = 0.006). In healthy donors, this Treg(EM) population constitutes only 2% of all Tregs (one to six Tregs per microliter) in peripheral blood but, when isolated, exhibit greater suppressive activity in vitro. With a median follow-up of 3.1 y (range 2.7-4.9 y) from sample acquisition, increased numbers of Treg(EM) cells proved to have independent prognostic importance in survival estimates, suggesting that enumeration of this Treg subset may be a more reliable indicator of immunological escape than FOXP3(+) T cells as a whole. Based on multivariate analyses, Treg(EM) impacted survival independently from myeloblast characteristics, cytopenias, karyotype, and comorbidities. Based on these findings, Treg(EM) cell expansion may be synonymous with human Treg activation and indicate microenvironmental changes conducive to transformation in myelodysplastic syndromes. The Journal of Immunology, 2012, 189:3198-3208.
Details
- Title: Subtitle
- Expansion of Effector Memory Regulatory T Cells Represents a Novel Prognostic Factor in Lower Risk Myelodysplastic Syndrome
- Creators
- Adam W. Mailloux - Moffitt Cancer CenterChiharu Sugimori - Moffitt Cancer CenterRami S. Komrokji - Moffitt Cancer CenterLili Yang - Moffitt Cancer CenterJaroslaw P. Maciejewski - Cleveland ClinicMikkael A. Sekeres - Cleveland ClinicRonald Paquette - University of California, Los AngelesThomas P. Loughran - Pennsylvania State UniversityAlan F. List - Moffitt Cancer CenterPearlie K. Epling-Burnette - Moffitt Cancer Center
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.189(6), pp.3198-3208
- DOI
- 10.4049/jimmunol.1200602
- PMID
- 22875800
- PMCID
- PMC3436939
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- Amer Assoc Immunologists
- Number of pages
- 11
- Grant note
- CA129952 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Genzyme Corporation; Sanofi-Aventis R01CA129952 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 09/15/2012
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297430202771
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