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CD4+ T Cells Expressing Latency-Associated Peptide and Foxp3 Are an Activated Subgroup of Regulatory T Cells Enriched in Patients with Colorectal Cancer
- Source :
- PLoS ONE, PLoS ONE, Vol 9, Iss 9, p e108554 (2014)
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- Latency-associated peptide (LAP) - expressing regulatory T cells (Tregs) are important for immunological self-tolerance and immune homeostasis. In order to investigate the role of LAP in human CD4⁺Foxp3⁺ Tregs, we designed a cross-sectional study that involved 42 colorectal cancer (CRC) patients. The phenotypes, cytokine-release patterns, and suppressive ability of Tregs isolated from peripheral blood and tumor tissues were analyzed. We found that the population of LAP-positive CD4⁺Foxp3⁺ Tregs significantly increased in peripheral blood and cancer tissues of CRC patients as compared to that in the peripheral blood and tissues of healthy subjects. Both LAP⁺ and LAP⁻ Tregs had a similar effector/memory phenotype. However, LAP⁺ Tregs expressed more effector molecules, including tumor necrosis factor receptor II, granzyme B, perforin, Ki67, and CCR5, than their LAP⁻ negative counterparts. The in vitro immunosuppressive activity of LAP⁺ Tregs, exerted via a transforming growth factor-β-mediated mechanism, was more potent than that of LAP⁻ Tregs. Furthermore, the enrichment of LAP⁺ Treg population in peripheral blood mononuclear cells (PBMCs) of CRC patients correlated with cancer metastases. In conclusion, we found that LAP⁺ Foxp3⁺ CD4⁺ Treg cells represented an activated subgroup of Tregs having more potent regulatory activity in CRC patients. The increased frequency of LAP⁺ Tregs in PBMCs of CRC patients suggests their potential role in controlling immune response to cancer and presents LAP as a marker of tumor-specific Tregs in CRC patients.
- Subjects :
- Male
lcsh:Medicine
T-Lymphocytes, Regulatory
Granzymes
Immune tolerance
Animal Cells
Transforming Growth Factor beta
Basic Cancer Research
Medicine and Health Sciences
Medicine
lcsh:Science
Aged, 80 and over
education.field_of_study
Multidisciplinary
digestive, oral, and skin physiology
FOXP3
Forkhead Transcription Factors
hemic and immune systems
Middle Aged
Gene Expression Regulation, Neoplastic
Oncology
Lymphatic Metastasis
Female
Tumor necrosis factor alpha
Cellular Types
Colorectal Neoplasms
Research Article
Receptors, CCR5
Immune Cells
Immunology
Population
chemical and pharmacologic phenomena
Peripheral blood mononuclear cell
Immune system
Biomarkers, Tumor
Immune Tolerance
Humans
Receptors, Tumor Necrosis Factor, Type II
Protein Precursors
education
Aged
Perforin
business.industry
lcsh:R
Biology and Life Sciences
Cancer
Cell Biology
equipment and supplies
medicine.disease
Granzyme B
Ki-67 Antigen
Case-Control Studies
lcsh:Q
Clinical Immunology
Peptides
business
Immunologic Memory
human activities
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....1f91f279e4687ca7770f908259ae632d