Zhu Mojun, Jin Zhaohui, Hubbard Joleen M
Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Cancers (Basel). 2021 Feb 6;13(4):651. doi: 10.3390/cancers13040651.
Microsatellite instability (MSI) is a hallmark of genetic predisposition to DNA damage. It arises from either germline or somatic events leading to impaired function of the mismatch repair system. It can be detected via genetic sequencing or immunohistochemistry with relatively high concordance rates. The presence of MSI in a tumor reflects a high neoantigen load and predicts favorable treatment response to immune checkpoint inhibitors (ICIs). In gastrointestinal cancers, MSI is a predictive biomarker for ICIs with potential prognostic impact but its clinical utility varies widely depending on tumor type. This may be explained by the complexity of tumor microenvironment as highlighted by recent translational studies. In this review, we will discuss the predictive and prognostic value of MSI status in non-colorectal cancers of the digestive system, important clinical trials involving ICIs and potential strategies to overcome resistance to immunotherapy.
微卫星不稳定性（MSI）是DNA损伤遗传易感性的一个标志。它源于种系或体细胞事件，导致错配修复系统功能受损。可通过基因测序或免疫组织化学检测，一致性率相对较高。肿瘤中MSI的存在反映了高肿瘤新抗原负荷，并预示着对免疫检查点抑制剂（ICI）有良好的治疗反应。在胃肠道癌症中，MSI是ICI的预测生物标志物，具有潜在的预后影响，但其临床效用因肿瘤类型而异。这可能是由近期转化研究强调的肿瘤微环境的复杂性所解释的。在本综述中，我们将讨论MSI状态在消化系统非结直肠癌中的预测和预后价值、涉及ICI的重要临床试验以及克服免疫治疗耐药性的潜在策略。
