Identification and characterization of regulatory T cell subsets infiltrated in human oral squamous cell carcinoma
Date Issued
2008
Date
2008
Author(s)
Hsu, Pei-Ju
Abstract
Oral squamous cell carcinoma (OSCC) accounts for more than 95% of all malignant neoplasms in the oral cavity, and ranks as the sixth major cause of cancer mortality in Taiwan. The high incidence of oral cancer is associated with the habit of chewing areca nut preparations. In addition to genotoxic effects and oncogenic mutations etc, immune-editing is currently regarded as one of the important etiological elements in human cancers. To investigate the distribution of regulatory T lymphocytes (Tregs) within tumor microenvironment in human oral squamous cell carcinoma (OSCC), the in vivo expressions of various Treg markers on tumor-infiltrating lymphocyte (TIL) was directly examined by flow cytometry. The results indicate that, in TIL, proportion of distinct CD25+ cells in the CD3+CD4+ subset (22.8±8.7%) were enriched relative to that found in PBMC (7.8 ±5.6 %) from OSCC patients (p<0.0001). FoxP3, a key transcription factor for CD4+CD25+ Tregs development and function, is correlated with the expression of CD25. Based on the expression intensity of CD25, different subsets of CD4+T cell were identified both in TIL and PBMC; CD25highFoxp3high, CD25intermediateFoxp3intermediate, and CD25lowFoxp3low. The CD25low or CD25intermediate subsets produced high or low amounts of IL-2 and IL-10, respectively, whereas CD25high subset scarcely produced these two cytokines. Another IL-10 secreting CD4+CD25-Foxp3-T cells, possibly Tr1 cells, could also be identified. CD4+CD25+Foxp3high Treg exhibits suppressive activity on the proliferation of autologous CD4+CD25- T cells. In coculture system, tumor stroma cells could enhance the production of IFN-γ、IL-2、TNF-α, but not IL-4 in CD3+ T cells. Therefore, there are different subsets of regulatory T cells infiltrated in OSCC.
Subjects
cancer immune-editing
oral squamous cell carcinoma
tumor-infiltrating lymphocyte
regulatory T lymphocytes
SDGs
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