Cancer Immunogenomics and immunotherapy

作者:肿瘤瞭望   日期:2017/4/7 15:34:44  浏览量:22647

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近年来高通量DNA测序技术的发展推动了基因组学研究的快速进展,为许多生物学问题提供了解决之径。

Yusuke Nakamura, MD,PhD 

Section of Hematology/Oncology, Department of Medicine
Department of Surgery, 
The University of Chicago, Chicago, IL 60637, USA
 
The recent development of high-throughput DNA sequencing technologies has driven the rapid progress in genomics research and enabled us to address a multitude of biological questions. It is clear that our immune system plays a critical role in various biological and pathological conditions, such as cancer, autoimmune diseases, and drug-induced toxicities. The recent development of cancer immunotherapies clearly demonstrates the importance of host immune cells, particularly drugs modulating the immune checkpoint molecules, in the fight against cancer. However, the molecular mechanisms by which these new therapies kill tumor cells still remain unclear.  Hence, we have explored the roll of newly-developed tools such as next generation sequencing in characterization of the immune system, which has been referred to as immunopharmacogenomics. This new field has enormous potential to help us better understand the changes/alterations to our immune responses during the course of cancer treatment. I here report the deep sequencing of T-cell receptors that will enable us to capture the molecular contribution of the immune system, including the immune microenvironment in tumors and its application for personalized TCR (T cell receptor)-engineered T cell treatment. 
 
近年来高通量DNA测序技术的发展推动了基因组学研究的快速进展,为许多生物学问题提供了解决之径。很明显,人体免疫系统在诸如癌症、自身免疫性疾病和药物诱导毒性等各种生理和病理反应中起关键作用。肿瘤免疫治疗的最新发展清楚地表明,宿主免疫细胞,特别是调节免疫检查点分子的药物在抗癌方面的重要性。然而,这些新疗法是如何杀死肿瘤细胞的分子机制仍不清楚。
 
因此,我们探索了新一代工具,如下一代测序技术在识别免疫系统表征方面的价值,我们称之为免疫药物基因组学。该新研究领域在帮助我们更好地了解肿瘤治疗过程中免疫反应的变化/改变方面有巨大的潜力。我在本次大会上报告了有助于明确免疫系统分子作用的T细胞受体深度测序,包括肿瘤的免疫微环境及其在工程T细胞治疗中的应用。

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