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FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions
- Publication Year :
- 2008
- Publisher :
- American Society of Hematology, 2008.
-
Abstract
- Regulatory T (Treg) cells are often found in human tumors; however, their functional characteristics have been difficult to evaluate due to low cell numbers and the inability to adequately distinguish between activated and Treg cell populations. Using a novel approach, we examined the intracellular cytokine production capacity of tumor-infiltrating T cells in the single-cell suspensions of enzymatically digested tumors to differentiate Treg cells from effector T cells. Similar to Treg cells in the peripheral blood of healthy individuals, tumor-infiltrating FOXP3+CD4 T cells, unlike FOXP3− T cells, were unable to produce IL-2 and IFN-γ upon ex vivo stimulation, indicating that FOXP3 expression is a valid biological marker for human Treg cells even in the tumor microenvironment. Accordingly, we enumerated FOXP3+CD4 Treg cells in intratumoral and peritumoral sections of metastatic melanoma tumors and found a significant increase in proportion of FOXP3+CD4 Treg cells in the intratumoral compared with peritumoral areas. Moreover, their frequencies were 3- to 5-fold higher in tumors than in peripheral blood from the same patients or healthy donors, respectively. These findings demonstrate that the tumor-infiltrating CD4 Treg cell population is accurately depicted by FOXP3 expression, they selectively accumulate in tumors, and their frequency in peripheral blood does not properly reflect tumor microenvironment.
- Subjects :
- Pathology
medicine.medical_specialty
medicine.medical_treatment
Immunology
Population
Cell
chemical and pharmacologic phenomena
Biology
Biochemistry
T-Lymphocytes, Regulatory
Aldesleukin
medicine
Humans
Lymphocyte Count
Neoplasm Metastasis
education
Immunobiology
Tumor microenvironment
education.field_of_study
Tumor-infiltrating lymphocytes
FOXP3
hemic and immune systems
Forkhead Transcription Factors
Cell Biology
Hematology
T lymphocyte
Cytokine
medicine.anatomical_structure
Cancer research
Cytokines
Multiple Myeloma
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....4a83dc5d992aae0a5ba2ffcb13fdb569