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首页> 外文期刊>Biochimica et biophysica acta. Reviews on cancer >Choosing tumor mutational burden wisely for immunotherapy: A hard road to explore
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Choosing tumor mutational burden wisely for immunotherapy: A hard road to explore

机译：明智地选择肿瘤突变负担，用于免疫疗法：探索的硬路

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摘要

Immunotherapy has revolutionized the treatment of cancer due to its remarkable efficacy and extensive survival benefit in multiple tumor types. However, predictive biomarkers are required to identify patients who are likely to respond to immunotherapy. Recently, tumor mutational burden (TMB) has been shown to be associated with clinical outcomes in diverse cancers, such as melanoma, non-small-cell lung cancer and colorectal cancer. Several studies have demonstrated that high TMB can effectively predict the objective response rate and progression-free survival, but the ability of TMB to predict overall survival is limited. Thus, the clinical utility of TMB as a predictive and prognostic biomarker in immunotherapy is currently controversial. Importantly, multiple factors can affect the accurate assessment of TMB and further interfere with its prediction of clinical outcomes. These factors include preanalytical factors such as sample status, analytical factors such as differences in platforms and methods for determining TMB and variability of cutoff values, and postanalytical factors such as inconsistent interpretation and reporting of results. In addition, the optimal definition and quantification of TMB are unclear and require harmonization and standardization for reliable clinical application. This review elaborates on the factors affecting TMB status in primary tumors, summarizes the clinical utility of TMB as a biomarker in immunotherapy, and evaluates the impact of each analysis stage on the accurate estimation of TMB, especially its quantification, aiming to facilitate TMB assessment in routine clinical settings.
机译：免疫疗法因其在多种肿瘤类型中的显着疗效和广泛的生存益处而彻底改变了癌症的治疗。然而，预测性生物标志物需要鉴定可能应对免疫疗法的患者。最近，肿瘤突变负担（TMB）已被证明与不同癌症的临床结果相关，例如黑素瘤，非小细胞肺癌和结肠直肠癌。几项研究表明，高TMB可以有效地预测客观反应率和无进展生存率，但TMB预测整体存活的能力是有限的。因此，TMB作为免疫疗法预测性和预测生物标志物的临床效用目前是有争议的。重要的是，多种因素可以影响TMB的准确评估，并进一步干扰其对临床结果的预测。这些因素包括预期的因素，如样本状态，分析因素，例如平台的差异以及确定TMB的方法和截止值的可变性，以及后期展示因素，如不一致的解释和结果。此外，TMB的最佳定义和定量尚不清楚，需要协调和标准化，可用于可靠的临床应用。本综述详细阐述了影响原发性肿瘤中TMB状态的因素，总结了TMB作为免疫疗法的生物标志物的临床效用，并评估每个分析阶段对TMB准确估计的影响，特别是其量化，旨在促进TMB评估的准确估算常规临床环境。

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  • 作者

    Li Rui; Han Dongsheng; Shi Jiping; Han YanXi; Tan Ping; Zhang Rui; Li Jinming;

  • 作者单位

    Chinese Acad Med Sci Natl Ctr Gerontol Natl Ctr Clin Labs Beijing Hosp Beijing Peoples R China;

    Chinese Acad Med Sci Natl Ctr Gerontol Natl Ctr Clin Labs Beijing Hosp Beijing Peoples R China;

    Chinese Acad Med Sci Natl Ctr Gerontol Natl Ctr Clin Labs Beijing Hosp Beijing Peoples R China;

    Chinese Acad Med Sci Natl Ctr Gerontol Natl Ctr Clin Labs Beijing Hosp Beijing Peoples R China;

    Chinese Acad Med Sci Natl Ctr Gerontol Natl Ctr Clin Labs Beijing Hosp Beijing Peoples R China;

    Chinese Acad Med Sci Natl Ctr Gerontol Natl Ctr Clin Labs Beijing Hosp Beijing Peoples R China;

    Chinese Acad Med Sci Natl Ctr Gerontol Natl Ctr Clin Labs Beijing Hosp Beijing Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

    Tumor mutational burden; TMB; Immunotherapy; Clinical utility; Cutoff;

    机译：肿瘤突变负担;TMB;免疫疗法;临床效用;截止;

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