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肿瘤突变负荷作为免疫检查点抑制剂应答生物标志物的疗效

英文原题:The Efficacy of Tumor Mutation Burden as a Biomarker of Response to Immune Checkpoint Inhibitors.

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The Efficacy of Tumor Mutation Burden as a Biomarker of Response to Immune Checkpoint Inhibitors.

PubMed 2023/04/04(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

癌症是全球主要死亡原因之一;因此,大量研究致力于探索潜在的治疗方法,包括免疫检查点抑制剂(ICIs)。最初,程序性死亡配体-1是用于预测ICIs疗效的生物标志物。然而,其在肿瘤微环境中的异质性表达——这对癌症进展至关重要——促进了对肿瘤突变负荷(TMB)的探索。在黑色素瘤和肺癌等多种癌症中的研究表明,高TMB与ICIs应答之间存在关联,提高了其预测价值。然而,TMB在众多其他癌症中未能预测ICI应答。因此,未来研究需要分析癌症类型之间的差异并建立TMB cutoff值,以便为临床使用TMB创建更标准化的方法。在本综述中,我们旨在探讨当前关于TMB作为生物标志物疗效的研究,讨论当前克服ICIs免疫耐药的方法,并强调该领域的新趋势,如液体活检、下一代测序、CAR-T 细胞疗法和个性化肿瘤疫苗。

展开英文摘要原文

Cancer is one of the leading causes of death in the world; therefore, extensive research has been dedicated to exploring potential therapeutics, including immune checkpoint inhibitors (ICIs). Initially, programmed-death ligand-1 was the biomarker utilized to predict the efficacy of ICIs.

However, its heterogeneous expression in the tumor microenvironment, which is critical to cancer progression, promoted the exploration of the tumor mutation burden (TMB). Research in various cancers, such as melanoma and lung cancer, has shown an association between high TMB and response to ICIs, increasing its predictive value.

However, the TMB has failed to predict ICI response in numerous other cancers.

Therefore, future research is needed to analyze the variations between cancer types and establish TMB cutoffs in order to create a more standardized methodology for using the TMB clinically. In this review, we aim to explore current research on the efficacy of the TMB as a biomarker, discuss current approaches to overcoming immunoresistance to ICIs, and highlight new trends in the field such as liquid biopsies, next generation sequencing, chimeric antigen receptor T-cell therapy, and personalized tumor vaccines.

论文信息

作者
Moeckel C、Bakhl K、Georgakopoulos-Soares I、Zaravinos A
第一作者单位
Department of Biochemistry and Molecular Biology, Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.United States
通讯作者单位
Department of Life Sciences, European University Cyprus, Diogenis Str., 6, Nicosia 2404, Cyprus.Cyprus
文献类型
综述
期刊
International journal of molecular sciences2023 Apr 4
原文标识
PubMed 37047684 · DOI 10.3390/ijms24076710