| Summary: | 碩士 === 國立中正大學 === 分子生物研究所 === 96 === Transitional cell carcinoma (TCC) is the most common cancer of the bladder. TCC can be diagnosed at an early stage and removed easily by transurethral resection of bladder tumor (TURBT), however highly frequent recurrences of this tumor within 6 months to one year after the surgery is difficult to handle. The host immune responses play important roles in TCC since the risk of recurrence can be reduced by intravesical bacillus Camette-Buerin (BCG) immunotherapy. The immune system not only can protect the host against tumor development but can also promote tumor growth through active tumor-induced immune tolerance. In this study, we investigated the interaction between tumor cells and host immune responses in bladder tumor patients. A group of 94 bladder cancer patients and 21 age-matched healthy controls were included in the present study. Our results showed that an increase of CD4+CD25+ Treg cells and decrease of CD56+ cells population was observed in TCC patients. IFN-gamma secreted from CD4, CD8 T cells and NK, NKT cells were down-regulated compared with age-matched controls, the systemic down-regulation of IFN-γ production in TCC patients caused the anti-tumor immunodeficiency. However, dysfunction of NK cytotoxicity was observed from fresh-isolated peripheral NK cells in TCC patients. Notably, the cytotoxic function of NK cells in TCC patients were diminished as well as the IFN-γ production. Moreover, the NK cells from TCC patients were more susceptible to tumor cell induced apoptosis, especially in IL-2 stimulation. The results of this study revealed that the bladder tumors increased the apoptosis of natural killer cells, lower the numbers of natural killer cells and impaired the natural killer cell functions. Besides, we found that predominant expression of IL-2 in peripheral T cells might drive NK cells activating and which resulted NK cells more susceptible to tumor cells induced apoptosis. This immuno-deficient condition in TCC patients may due to the inhibition of innate immune cells-NK cells by tumor cells. According to this study, clinical treatment of TCC patients with IL-2 should be further evaluated. It suggested that altered innate immunity may contribute the bladder tumor incidence. It indicated that NK cells may be as a target for immunotherapy of TCC patients.
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