Head and Neck Surgery, National Institute of Oncology, Budapest, Hungary.
Curr Drug Targets. 2021;22(9):968-976. doi: 10.2174/1389450122666210325121322.
The microsatellite instable phenotype resulting from errors in DNA mismatch repair proteins accounts for as far as 15 to 20% of non-hereditary colon cancers but is scarce in rectal cancer. It has been shown that the increased existence of tumor-specific neoantigens in hypermutated tumors is correlated with higher tumor-infiltrating lymphocytes (TILs) and overexpression of immune checkpoint receptors and ligands, mainly PD-1 and PD-L1. In particular, the data gained up to now gives evidence that neoantigen recognition constitutes a dominant component in the course of immunotherapies. This review's primary objective is to describe current approvals and summarize present knowledge about the outcomes of immuno-oncology treatment of microsatellite instable colorectal cancer (CRC). The secondary objective is to give a narrative report about testing methodologies, prognostics, and the predictive value of microsatellite instability. For this purpose, a literature review was performed, focusing on published clinical trial results, ongoing clinical trials and timelines, testing methods, and prognostic and predictive value of MSI. Following four recent FDA approvals of immunotherapy of MSI-high CRC, further work should be warranted by pathology societies towards standardization and rising concordance and reproducibility across the IHC/MSI testing landscape in order to facilitate professionals to offer better survival options for patients with CRC.
由 DNA 错配修复蛋白错误导致的微卫星不稳定表型占非遗传性结肠癌的 15%至 20%，但在直肠癌中很少见。已经表明，在高突变肿瘤中存在更多的肿瘤特异性新抗原与更高的肿瘤浸润淋巴细胞 (TILs) 和免疫检查点受体和配体的过度表达有关，主要是 PD-1 和 PD-L1。特别是，到目前为止获得的数据表明，新抗原识别构成免疫疗法过程中的主要组成部分。本综述的主要目的是描述当前的批准情况，并总结关于免疫肿瘤学治疗微卫星不稳定结直肠癌 (CRC) 的现有知识。次要目的是对检测方法、预后和微卫星不稳定性的预测价值进行叙述性报告。为此，进行了文献回顾，重点关注已发表的临床试验结果、正在进行的临床试验和时间表、检测方法以及 MSI 的预后和预测价值。在最近四项 FDA 批准免疫疗法治疗 MSI 高 CRC 后，病理学会应该进一步努力实现标准化，并提高免疫组化/微卫星不稳定性检测领域的一致性和重现性，以方便专业人员为 CRC 患者提供更好的生存选择。
