AUTHOR=Zeng Tian , Zhang Lei , Chen Can , Zhao Xiang , Liu Xiaoqing , Ran Fengwei , Yong Tingting , Yang Ying , Zhang Henghui , Zhang Yanling 

TITLE=Durable Complete Response to Pembrolizumab in Esophageal Squamous Cell Carcinoma With Divergent Microsatellite Status: A Case Report

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.767957

DOI=10.3389/fonc.2021.767957

ISSN=2234-943X

ABSTRACT=Microsatellite instability-high (MSI-H) is widely believed as a biomarker for immune checkpoint inhibitors (ICIs) such as pembrolizumab in solid tumors. However, due to the low prevalence of MSI-H in most cancers, it tends to be insufficient to identify appropriate patients for receiving ICIs according to this biomarker alone. Here we reported a Chinese esophageal squamous-cell carcinoma (ESCC) patient with unusual divergent MSI status between primary lesion (MSS) and metastasis (MSI-H) developed after platinum-based therapy and radiotherapy. Both his primary and metastatic tumors responded well to pembrolizumab-containing therapies or pembrolizumab monotherapy and maintained complete response for over 24 months. Whole exome sequencing and multiplex immunohistochemistry were used to examine his tissue specimens. Notably, there were multiple high-frequency mutations of DDR (DNA damage repair) genes shared in primary lesion and metastasis, especially in the latter. Besides, we observed considerable degrees of infiltrating CD3+/CD8+ lymphocytes in both of his primary tumor and metastasis without obvious difference, suggesting that the conversion of microsatellite status had little effect on the infiltration of lymphocytes. Collectively, given the predictive role of DDR alterations for ICIs in other malignancies, the alterations of DDR genes might be also promising biomarkers in ESCC individuals receiving ICIs.