透過卵巢癌病人檢體及動物模式探討卵巢癌生成過程中宿主免疫力的動態改變並評估其可逆之因素

Exploration of the kinetic alterations of host immunities and their reversible factors in the progression of ovarian cancer through the specimens of ovarian cancer patients and the animal model of ovarian carcinoma

陳宇立(Yu-Li Chen)

指導教授 ： 錢宗良

國立臺灣大學/醫學院/解剖學暨細胞生物學研究所/博士(2013年)

https://doi.org/10.6342/NTU.2013.00244

摘要

根據台灣衛生署的統計，卵巢癌的發生率逐年升高，其死亡率在婦女的惡性腫瘤中名列第一。卵巢癌的五年總存活率為45%，依不同期別及不同組織型態而有不同。若腫瘤只出現在卵巢或侷限於骨盆腔時，其存活率分別為93%及69%，但大部分病患(約68%)在診斷時即出現遠端轉移，其五年存活率便只剩30%。
在很多文獻已經證實，卵巢癌細胞是具有誘發出宿主抗腫瘤的免疫能力。當身體內增進及抑制免疫反應的機制失衡時，體內對抗腫瘤的免疫力便會被破壞。藉由卵巢癌病人檢體及其動物模式的分析，可以了解卵巢癌生成過程中宿主促進及抑制免疫力的動態改變，同時可以發現在腫瘤形成過程中，與病人預後相關以及具有可逆性的因子。
我們在動物實驗中發現，當抑制調控性T細胞的功能，可以矯正在腫瘤形成過程中，宿主體內增進及抑制免疫反應失衡的情況，並產生有效的抗腫瘤效果。透過病人檢體的分析，能夠發現，當卵巢癌病患的腹水中，如果表現較高的干擾素-γ，這些病人將會有較差的存活率。因此，探究新的方式來抑制調控性T細胞的功能，可以成為癌症免疫治療的一個重要方式。此外，卵巢癌病患的腹水中，干擾素-γ的表現程度，可以成為與病人預後相關的標記，也可以成為日後與干擾素-γ相關之癌症免疫治療的重要參考。

關鍵字

卵巢癌 ； 腫瘤免疫

並列摘要

According to the statistics of the Department of Health, the incidence of ovarian cancer increased in recent years and the mortality rate is highest in all gynecologic malignancies in Taiwan. The 5- year relative survival rate is 45% overall, but varies by stage and histologic type. Women with the localized or regional diseases such as pelvic cavity have the survival rates of 93% and 69%, respectively, but most cases (~68%) diagnosed as distant stage have overall 5-year relative survival rate of 30%.
Ovarian carcinoma has been proven to be immunogenic in the previous reports. When the imbalance between immune activation and suppression occurs, the immune responses against tumor cells are destroyed. Through the analysis of clinical specimens of ovarian cancer patients and animal model of ovarian carcinoma, the kinetic alterations of host immunities and their reversible and prognostic factors in the progression of ovarian cancer could be identified.
In the animal experiments, depletion of regulatory T (Treg) cells can correct the imbalance of immunologic profiles and generate potent anti-tumor effects. The patients with ovarian cancer and higher interferon-gamma (IFN-γ) levels in the ovarian cancer-associated ascites have poorer survival. Therefore, the exploration of new strategies for effective depletion of Treg cells could become an important modality for cancer immunotherapy. In addition, IFN-γ expression levels in ascites could be a prognostic marker and a potential reference for future immunotherapy targeting IFN-γ.

並列關鍵字

ovarian carcinoma ； tumor immunology

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