Lon蛋白酶(Lon)是線粒體基質中一種主要的蛋白酶，其上調與腫瘤微環境中、活性氧化物質(ROS)的增加有關。Lon的上調會使周圍環境變成慢性發炎症環境，這種環境不僅適合腫瘤生長，而且對免疫細胞也有抑制作用。介白素10 (IL-10) 是一種細胞因子，主要透過抗發炎作用來調節先天性和後天性免疫反應，IL-10 即是免疫抑制的指標。在本論文，我們發現腫瘤細胞能透過Lon來調節IL-10分泌的能力，以建立免疫抑制的腫瘤微環境。在我們之前的結果，地塞米松 (dexamethasone) 可誘導調節型樹突細胞 (DC) 中Il10 和Lon基因表現。在本論文研究中，我們的實驗結果顯示，當Lon在癌細胞中過量表現時，癌細胞中il10的表現量水平會增加。我們還觀察到Lon透過 ROS 所調控的 STAT3以及P38 MAPK 細胞訊號途徑調節il10表達。除此之外，我們也發現癌細胞Lon上調時，會促使癌細胞增加介白素6 (IL-6) 表現，然後增強誘導il10的表現。因此，Lon可以透過不同方式調節il10的表現分泌。進一步發現，在體外細胞模式模擬Lon過表現的腫瘤微環境條件下，癌細胞的Lon高表現狀態會調節DC並使其表抗發炎的特性。綜合上述，本論文的結果發現Lon參與了腫瘤免疫抑制微環境的塑造，並誘導DC使其表現出免疫抑制的表型。

Lon protease (Lon) is a major protease in mitochondria whose upregulation links to an increase of reactive oxidative species (ROS) in the tumor microenvironment (TME). Upregulation of mitochondrial Lon will change peripheral surroundings into an environment of chronic inflammation, this environment is not only suitable for tumor growth but also suppressive for immune cells. Interleukin-10 (IL-10) is a cytokine modulates both innate and adaptive immunity, primarily by exerting anti-inflammatory effects, we can say IL-10 is a hallmark of immunosuppression. In this case, we proposed Lon has ability to regulate IL-10 secretion in the cancer cells due to their target to establish an immunosuppressive environment. Following, in our recent results, there is a correlated expression between Il10 and Lon in Dexamethasone-induced regulatory type dendritic cells (DCs). In this study, we show that il10 expression level is upregulated in cancer cell lines when overexpressed with Lon. Beyond, we also observed Lon regulates il10 expression via ROS-dependent STAT3-P38 MAPK pathway. Furthermore, cancer cells enhance their ability producing IL-10 after treating with rIL-6, which is a factor that would be increased upon Lon-upregulation. Hence, it is supported that Lon could positively regulate the secretion of IL-10. We further found DCs showed elevated Lon expression accompanied with anti-inflammatory phenotypes under Lon-overexpressed condition. Taken together, this study showed another role of Lon in participating in shape up of anti-inflammatory condition that may be suitable for tumor growth meanwhile suppressive for anti-tumor immunity.

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