轉移性大腸直腸癌患者之MMR、PD-L1及TIL表現的關聯性以及存活因子研究

Study on Correlation Among Manifestations and Survival Factors in Patients with Metastatic Colorectal Cancer

張景明(Ching-Ming Chang) ； 吳佩儒(Pei-Ju Wu) ； 許維中(Wei-Chung Hsu)

《澄清醫護管理雜誌》 16卷3期 (2020/07) Pp. 9-22

摘要

目的：近年來免疫檢查哨抑制劑（Immune Checkpoint Inhibitor, ICI）發展迅速，但對於大腸直腸癌，直到近期才發現核酸錯誤配對修復（Mismatch Repair, MMR）缺陷的病患，對於免疫檢查哨抑制劑的治療效果特別好；在許多癌症研究中，腫瘤細胞上PD-L1表現（Tumor Cell PDL1, TC-PDL1）的多寡可預測免疫檢查哨抑制劑的治療效果；再者，腫瘤浸潤淋巴球（Tumor-Infiltrating Lymphocytes, TIL）的多寡在許多癌症扮演重要的預後功能。因此，本研究目的在於分析免疫學相關的生物指標（MMR、TC-PDL1、TIL）的關聯性，並做上述生物指標於轉移性大腸直腸癌的預後探討。方法：本研究共收集了93位轉移性大腸直腸癌的患者的臨床基本資料，並以免疫組織化學染色法分析腫瘤組織切片的MMR（MLH-1、MSH-2、MSH-6、PMS2）、TC-PDL1、TIL等的表現，並運用統計方法進行相關性分析，以及對相關變數進行存活分析。結果：相關性分析發現，不論是MMR & TC-PDL1、MMR & TIL或是TIL & TC-PDL1，兩兩間皆無相關性。存活分析方面，以多變數分析結果發現TIL為最重要的存活預後因子。結論：在免疫治療的時代中，MMR、TC-PDL1、TIL三者在轉移性大腸直腸癌各有其角色，應常規性檢測，而TIL+為預後較佳之因子，建議將來需要有更大病患人數規模，並加入免疫檢查哨抑制劑治療的隨機對照前瞻性研究，以深入了解免疫治療時代中，重要的預測與預後因子。

關鍵字

轉移性大腸直腸癌 ； 核酸錯誤配對修復 ； 細胞程式死亡－配體1 ； 腫瘤浸潤淋巴球

並列摘要

Purposes: In recent years, the development of immune checkpoint inhibitors has progressed rapidly. Immune checkpoint inhibitors therapy is particularly effective in patients with metastatic colorectal cancer with defective mismatch repair (MMR). In previous cancer studies, the expression level of tumor cell PDL1 (TC-PDL1) has helped to predict the therapeutic effect of immune checkpoint inhibitors; additionally, the number of tumor-infiltrating lymphocytes (TIL) has been found to play an important prognostic role in many cancers. Therefore, the present study aimed to analyze the correlation among immunology-related biomarkers (MMR, TC-PDL1, and TIL) and explore the use of the aforementioned biomarkers in predicting the prognosis of metastatic colorectal cancer. Methods: In this study, basic clinical information was collected from 93 patients with metastatic colorectal cancer. Immunohistochemical staining was used to analyze the expression of MMR (MLH-1, MSH-2, MSH-6, and PMS2), TC-PDL1, and TIL in tumor tissue sections. Statistical methods were used for performing correlation and survival analyses based on relevant variables. Results: Correlation analysis revealed that there was no correlation between MMR and TC-PDL1, MMR and TIL, or TIL and TC-PDL1, whereas multivariate analysis showed that TIL was the most important prognostic factor for survival. Conclusions: Routine detection of MMR, PD-L1, and TIL should be performed, since they play important role in predicting the prognosis of metastatic colorectal cancer. Among these markers, TIL+ is a factor that indicates better prognosis. It is suggested that future studies should enroll a larger number of patients and randomized controlled prospective studies on immune checkpoint inhibitors should be conducted to further elucidate the important predictive and prognostic factors for metastatic colorectal cancer following immunotherapy.

並列關鍵字

Metastatic colorectal cancer ； Mismatch repair ； Cell programmed death-ligand 1 ； Tumor-infiltrating lymphocytes