Characterization of tumor infiltrating regulatory T cells and the interplay with Th17 cells in human oral squamous cell carcinoma

碩士 === 國立臺灣大學 === 微生物學研究所 === 97 === Oral squamous-cell carcinoma (OSCC) was the sixth most common cancer worldwide with low survival rates after therapy. Immunosuppression mediated by CD4+CD25highFoxp3+ regulatory T (Treg) cells was a characteristic feature of OSCC. Recent studies have defined two...

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Bibliographic Details
Main Authors: Wan-Ling Lai, 賴宛伶
Other Authors: 賈景山
Format: Others
Language:zh-TW
Published: 2009
Online Access:http://ndltd.ncl.edu.tw/handle/86035762591005039316
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Summary:碩士 === 國立臺灣大學 === 微生物學研究所 === 97 === Oral squamous-cell carcinoma (OSCC) was the sixth most common cancer worldwide with low survival rates after therapy. Immunosuppression mediated by CD4+CD25highFoxp3+ regulatory T (Treg) cells was a characteristic feature of OSCC. Recent studies have defined two subsets of FOXP3+ natural Treg cells by the expression of the costimulatory molecule ICOS and IL-10 or TGF-b. Our previous study revealed that proportion of CD4+CD25highFoxp3+ Treg cells in TIL were significantly enriched relative to that found in PBMC from OSCC patients. Moreover, there were different subsets of regulatory T cells infiltrated in OSCC. The specific aim was to identify and characterize the different subsets of Tregs in TIL based on ICOS expression. In addition, association of Tregs with the presence of Th17 cells was also investigated to confirm whether there was synergistic or antagonistic relationship between these cells in TIL of OSCC. Despite the important role of Th17 cells in the pathogenesis of many autoimmune diseases, their prevalence and the mechanisms by which they are generated and regulated in cancer remain unclear. A recent study found that the tumor-associated Th17 cells and Treg cells were synchronically increased following tumor development. The kinetic distribution of Treg cells and Th17 cells suggested their close relationship in the tumor. In this study, we reported that the high percentage of CD4+IL-17+ cells and IL-17+Foxp3+ cells in the tumor site, compared with the low percentage of CD4+IL-17+ cells and IL-17+Foxp3+ cells in PBMC from healthy donor and cancer patient. These finding consisted with the high level of IL-1β、IL-6、TGF-β presented in the tumor microenvironment. Moreover, this study also found the prevalence of IL-17+Foxp3+ cells and Th17 cells were high positive correlation, and the prevalence of Th17 cells and Foxp3 cells were high negative correlation in the tumor site. To further demonstrate the role of tumor cells in the induction of IL-17+Foxp3+ cells, the in vitro coculture system were performed. The results show coculture of PBMC with tumor cells could generate high percentage of Th17 cells and IL-17+Foxp3+ cells. It has been reported that viable bacteria presented within oral squamous cell carcinoma tissue. The correlation between Th17 cells generation and bacteria infection in OSCC needs further investigation.