He Yin, Liu Zhi-Xian, Jiang Ze-Hang, Wang Xiao-Sheng
Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, Nanjing 211198, Jiangsu Province, China.
World J Gastrointest Oncol. 2019 Apr 15;11(4):270-280. doi: 10.4251/wjgo.v11.i4.270.
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.
胃肠道（GI）癌症普遍存在，在全球范围内导致极高的癌症死亡人数。传统的治疗策略，包括手术、化疗、放疗和靶向治疗，对晚期胃肠道癌症的治疗效果有限。最近，免疫疗法在治疗各种难治性恶性肿瘤方面显示出前景，包括错配修复缺陷（dMMR）或微卫星不稳定（MSI）的胃肠道癌症。因此，免疫疗法可能是胃肠道癌症一种有前景的治疗方法。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，发现预测生物标志物以对胃肠道癌症患者对免疫疗法的反应进行分层很重要。某些基因组特征，如dMMR/MSI、肿瘤突变负荷（TMB）和肿瘤非整倍体，已与肿瘤免疫和免疫疗法反应相关，并可能作为癌症免疫疗法的预测生物标志物。在本综述中，我们研究了肿瘤免疫与三种基因组特征之间的相关性：dMMR/MSI、TMB和肿瘤非整倍体。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和低肿瘤非整倍体与胃肠道癌症中肿瘤免疫升高相关。为了提高胃肠道癌症的免疫治疗潜力，需要识别更多与肿瘤免疫反应相关的遗传或基因组特征。此外，探索不同免疫治疗方法的联合以及免疫疗法与其他癌症治疗方法的联合是值得的。
