Mismatch repair-based stratification for immune checkpoint blockade therapy

American Journal of Cancer Research

Yang Peng¹  Lihong Zhang² 

[1] Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

关键词: Mismatch repair;    microsatellite instability;    immune checkpoint blockade;    programmed cell death protein 1;    next-generation sequencing;    gene signature;   

DOI  :  

学科分类：肿瘤学

来源: e-Century Publishing Corporation

【 摘 要 】

Mismatch repair (MMR) plays a key role in maintaining genomic stability. Mismatch repair deficiency (MMR-D) causes a molecular feature of microsatellite instability (MSI) and contributes to the development of human cancers and genetic diseases with cancer predisposition such as Lynch syndrome. Recent studies have shown that immune checkpoint blockade therapy has a promising response in MMR-D cancers regardless of the tissue of origin. Being able to identify patients with MMR-D cancers is an important challenge in clinical practice. Although immunohistochemistry (IHC) and polymerase chain reaction (PCR)-based MSI analysis combined with a subsequent MMR gene test are used as the standard of care in the clinical setting to identify patients with MMR-D cancers, these methods have limitations as a pan-cancer testing strategy. Next-generation sequencing (NGS) has developed and matured as a clinical option and NGS has advantages for use as a novel testing strategy for MMR-D detection. In this review, we describe the genetic basis of MMR-D, current diagnostic algorithms in the clinical management of MMR-D, the novel NGS approach, and potential detection strategy of anti-cancer immunity biomarkers of MMR-D.

【 授权许可】

CC BY-NC