以模擬腫瘤間質組織之微流道平台評估胞殺性T淋巴球之抗癌作用

Abstract

腫瘤抗原特異性之胞殺性T淋巴球媒介之抗癌免疫反應在癌症的免疫療法中扮演重要的角色。然而，雖然已有大量的研究顯示腫瘤組織會釋放化學物質以逃脫免疫系統的抗癌反應，但是腫瘤組織周圍緻密的膠原蛋白基質以及升高的組織間質液壓等物理性屏障對於胞殺性T淋巴球阻礙卻經常被忽略。在本研究中，我們發展了一個能夠模擬腫瘤組織微環境的微流道平台。我們使用此裝置研究了在物理性屏障存在的情況下胞殺性T淋巴球之細胞移行特性。此外，我們以量化的方法評估胞殺性T淋巴球在對於特異性目標及非特異性目標之抗癌免疫反應。

Tumour antigen-specific CD8+ cytotoxic T lymphocyte (CTL)-mediated killing of tumour cells plays a crucial role in cancer immunotherapy. However, while a multitude of chemical factors employed by cancers to escape from anticancer immunity are disclosed, little attention thus far has been paid to the physical barriers established by tumours in their interstitium such as dense collagenous matrix and high interstitial fluid pressure (IFP), which also poses a significant challenge to CTLs to successfully contact the targeting cells. In this study, we developed a platform which can mimic the microenvironment of solid tumors. And we used the device to investigate the transmigration characteristics of CTLs at the presence of the physical barriers and quantitatively evaluated the performance of CTL-mediated anti-cancer immune response when the cancer cells were specifically and non-specifically targeted.