Chang Liisa, Chang Minna, Chang Hanna M, Chang Fuju
Department of Medicine, Medway NHS Foundation Trust, Gillingham, Kent.
Faculty of Medicine, Imperial College London, South Kensington Campus.
Appl Immunohistochem Mol Morphol. 2018 Feb;26(2):e15-e21. doi: 10.1097/PAI.0000000000000575.
Immunotherapy has shown promising results in various types of cancers. Checkpoint inhibitor drugs developed for cancer immunotherapy have been approved by the US Food and Drug Administration (FDA) for patients with advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin lymphoma. In the latest announcement, the FDA has granted accelerated approval to pembrolizumab for pediatric and adult patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient solid tumors. This is the first time the agency has approved a cancer treatment based on a common biomarker rather than organ-based approach. MSI-H, either due to inherited germline mutations of mismatch repair genes or epigenetic inactivation of these genes, is found in a subset of colorectal and noncolorectal carcinomas. It is known that MSI-H causes a build up of somatic mutations in tumor cells and leads to a spectrum of molecular and biological changes including high tumor mutational burden, increased expression of neoantigens and abundant tumor-infiltrating lymphocytes. These changes have been linked to increased sensitivity to checkpoint inhibitor drugs. In this mini review, we provide an update on MSI-related solid tumors with special focus on the predictive role of MSI for checkpoint immunotherapy.
免疫疗法在各类癌症中已显示出有前景的结果。为癌症免疫疗法研发的检查点抑制剂药物已获美国食品药品监督管理局（FDA）批准，用于晚期黑色素瘤、非小细胞肺癌、肾细胞癌、膀胱癌及难治性霍奇金淋巴瘤患者。在最新公告中，FDA已加速批准帕博利珠单抗用于患有微卫星高度不稳定（MSI-H）或错配修复缺陷实体瘤的儿科和成年患者。这是该机构首次基于常见生物标志物而非基于器官的方法批准一种癌症治疗药物。MSI-H要么是由于错配修复基因的遗传性种系突变，要么是这些基因的表观遗传失活，在一部分结直肠癌和非结直肠癌中被发现。已知MSI-H会导致肿瘤细胞中体细胞突变的积累，并引发一系列分子和生物学变化，包括高肿瘤突变负荷、新抗原表达增加以及丰富的肿瘤浸润淋巴细胞。这些变化与对检查点抑制剂药物的敏感性增加有关。在本综述中，我们提供了MSI相关实体瘤的最新情况，特别关注MSI在检查点免疫治疗中的预测作用。
