2016-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/658404摘要：癌症的免疫治療在單株抗體PD-1 及PD-L1 的開發之後，以及其在黑色素瘤的治療成效，目前已經逐漸展開。目前關於大腸直腸癌的免疫治療仍屬萌芽階段。許多基本問題仍待釐清，例如：具有哪些生物特性的腫瘤較為有效？其真正原理在何處？而最終也必須仰賴更多的臨床試驗才能全盤了解免疫治療的優點及缺點。本計畫為三年期的計畫，在第一年，我們擬在我們的兩千份組織庫中篩選出約200 份，具微小衛星不穩定生物特性的腫瘤，並以免疫螢光染色的方法偵測hMSH2、hMLH1、hMSH6、hPMS2 的表現來確定微小衛星不穩定確實存在於大腸直腸癌組織之中。並分析先前接受各種不同化學治療如5-FU、Oxaliplatin、或irinotecan 的化學治療敏感度；第二年，我們會分析這些具微小衛星不穩定腫瘤之PD-L1 表現量，以及腫瘤四周浸潤之淋巴球的表面標誌如：CD-8和PD-1 的表現，以評估微小衛星不穩定與腫瘤本身對人體T 淋巴球的免疫反應強弱，如此便可初步鑑定出哪一類的大腸直腸癌較適合以抗PD-1 或PD-L1 的單株抗體來做免疫治療；第三年，我們擬應用第一年及第二年的研究成果，將推測中具免疫治療較有效之生物特性的臨床MSI 病人 (n=20) 來做前瞻性研究。以將此免疫治療能夠實際應用於某一次群的大腸直腸癌病患。我們深信，對台灣大腸直腸癌的精準治療，將會做出實際的貢獻。<br> Abstract: With the emergence of monoclonal antibody PD-1 and PD-L1, and encouraged by their treatmentefficacy on malignant melanoma, the immunotherapy for the solid tumor has been underway.However, the immunotherapy for colorectal cancer is still in the initiating stage. Many basicproblems remain unknown and need to be clarified, such as what tumor subset will be beneficialfrom immunotherapy and the underlying mechanism, and to comprehensively understand theadvantage and drawbacks of immunotherapy for colorectal cancer, the clinical trial is ultimatelyneeded.This is a three-year project. In the first year: we plan to screen 200 colorectal cancer withmicrosatellite instability from our tissue bank, by the immunocytochemistry of the hMSH2, hMLH1,hMSH6, hPMS2 to define the presence of microsatellite instability. Simultaneously, the prognosissignificance of these proteins and their association with the chemosensitivity of 5-FU, Oxaliplatin,and irinotecan will also be investigated; In the second year, we will analyze the expression of PD-L1in the tumor tissue with microsatellite instability and the PD-1 expression of the tumor infiltratingcytotoxic T-lymphocyte (CD-8). Through this procedure, we can evaluate the immune response ofcolorectal cancer with microsatellite instability to their microenvironment, and therefore we canidentify the tumor subset that will be potentially suitable for immunotherapy; In the third year, wewill prospectively recruit clinical patients (n=20) with the favorable biomarker (MSI) to conduct aclinical trial for immunotherapy, and so that the clinical implication of such treatment modality willbe further clarified.We believe that the present three year project will practically contribute to the precision therapy ofcolorectal cancer in Taiwan.大腸直腸癌免疫治療MSIMMR 基因PD-1PD-L1colorectal cancerimmunotherapyMSIMMR genePD-1PD-L1