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Identification of genomic features associated with immunotherapy response in gastrointestinal cancers

机译:鉴定与胃肠道癌症免疫治疗反应相关的基因组特征

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摘要

Gastrointestinal (GI) cancers prevail and account for an extremely high number of cancer deaths worldwide. The traditional treatment strategies, including surgery, chemotherapy, radiotherapy, and targeted therapy, have a limited therapeutic effect for advanced GI cancers. Recently, immunotherapy has shown promise in treating various refractory malignancies, including the GI cancers with mismatch repair deficiency (dMMR) or microsatellite instability (MSI). Thus, immunotherapy could be a promising treatment approach for GI cancers. Unfortunately, only a small proportion of GI cancer patients currently respond to immunotherapy. Therefore, it is important to discover predictive biomarkers for stratifying GI cancer patients response to immunotherapy. Certain genomic features, such as dMMR/MSI, tumor mutation burden (TMB), and tumor aneuploidy have been associated with tumor immunity and im-munotherapy response and may serve as predictive biomarkers for cancer immunotherapy. In this review, we examined the correlations between tumor immunity and three genomic features: dMMR/MSI, TMB, and tumor aneuploidy. We also explored their correlations using The Cancer Genome Atlas data and confirmed that the dMMR/MSI status, high TMB, and low tumor aneuploidy are associated with elevated tumor immunity in GI cancers. To improve the immunotherapeutic potential in GI cancers, more genetic or genomic features associated with tumor immune response need to be identified. Furthermore, it is worth exploring the combination of different immunotherapeutic methods and the combination of immunotherapy with other therapeutic approaches for cancer therapy.
机译:胃肠道(GI)癌症盛行,并导致全世界癌症死亡人数极高。传统的治疗策略,包括手术,化学疗法,放疗和靶向治疗,对于晚期胃肠道癌的治疗效果有限。最近,免疫疗法已显示出治疗各种难治性恶性肿瘤的希望,包括具有失配修复缺陷(dMMR)或微卫星不稳定性(MSI)的胃肠道癌症。因此,免疫疗法可能是胃肠道癌症的一种有前途的治疗方法。不幸的是,目前只有一小部分胃肠道癌症患者对免疫疗法有反应。因此,重要的是发现预测性生物标记物,以对胃肠道癌患者对免疫疗法的反应进行分层。某些基因组特征,例如dMMR / MSI,肿瘤突变负担(TMB)和肿瘤非整倍性已与肿瘤免疫力和免疫疗法反应相关,并可作为癌症免疫疗法的预测生物标志物。在这篇综述中,我们研究了肿瘤免疫力与三个基因组特征之间的相关性:dMMR / MSI,TMB和肿瘤非整倍性。我们还使用《癌症基因组图谱》数据探索了它们之间的相关性,并证实dMMR / MSI状态,高TMB和低肿瘤非整倍性与GI癌症中的肿瘤免疫力升高相关。为了提高胃肠道癌症的免疫治疗潜力,需要确定更多与肿瘤免疫反应相关的遗传或基因组特征。此外,值得探索不同免疫治疗方法的结合以及免疫治疗与其他癌症治疗方法的结合。

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