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

Microsatellite instability-high (MSI-H) is widely believed to be 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 whether patients should receive ICIs accord...

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Autores principales:	Tian Zeng, Lei Zhang, Can Chen, Xiang Zhao, Xiaoqing Liu, Fengwei Ran, Tingting Yong, Ying Yang, Henghui Zhang, Yanling Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	esophageal squamous cell carcinoma microsatellite instability pembrolizumab complete response DNA damage repair Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e2b5abf2a3bf42fe98dacd41ae6af75e
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spelling	oai:doaj.org-article:e2b5abf2a3bf42fe98dacd41ae6af75e2021-11-19T10:47:26ZDurable Complete Response to Pembrolizumab in Esophageal Squamous Cell Carcinoma With Divergent Microsatellite Status: A Case Report2234-943X10.3389/fonc.2021.767957https://doaj.org/article/e2b5abf2a3bf42fe98dacd41ae6af75e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.767957/fullhttps://doaj.org/toc/2234-943XMicrosatellite instability-high (MSI-H) is widely believed to be 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 whether patients should receive ICIs according to this biomarker alone. Here, we report a Chinese esophageal squamous cell carcinoma (ESCC) patient with unusual divergent MSI status between the primary lesion (MSS) and metastatic lesion (MSI-H) which developed after platinum-based therapy and radiotherapy. Both his primary and metastatic tumors responded well to pembrolizumab-containing therapies or pembrolizumab monotherapy and maintained a 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 the primary lesion and metastatic lesion, especially in the latter. Besides, we observed considerable degrees of infiltrating CD3+/CD8+ lymphocytes in both of his primary tumor and metastatic tumor 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 also be promising biomarkers in ESCC individuals receiving ICIs.Tian ZengLei ZhangCan ChenXiang ZhaoXiaoqing LiuFengwei RanTingting YongYing YangHenghui ZhangHenghui ZhangHenghui ZhangYanling ZhangFrontiers Media S.A.articleesophageal squamous cell carcinomamicrosatellite instabilitypembrolizumabcomplete responseDNA damage repairNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	esophageal squamous cell carcinoma microsatellite instability pembrolizumab complete response DNA damage repair Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	esophageal squamous cell carcinoma microsatellite instability pembrolizumab complete response DNA damage repair Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Tian Zeng Lei Zhang Can Chen Xiang Zhao Xiaoqing Liu Fengwei Ran Tingting Yong Ying Yang Henghui Zhang Henghui Zhang Henghui Zhang Yanling Zhang Durable Complete Response to Pembrolizumab in Esophageal Squamous Cell Carcinoma With Divergent Microsatellite Status: A Case Report
description	Microsatellite instability-high (MSI-H) is widely believed to be 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 whether patients should receive ICIs according to this biomarker alone. Here, we report a Chinese esophageal squamous cell carcinoma (ESCC) patient with unusual divergent MSI status between the primary lesion (MSS) and metastatic lesion (MSI-H) which developed after platinum-based therapy and radiotherapy. Both his primary and metastatic tumors responded well to pembrolizumab-containing therapies or pembrolizumab monotherapy and maintained a 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 the primary lesion and metastatic lesion, especially in the latter. Besides, we observed considerable degrees of infiltrating CD3+/CD8+ lymphocytes in both of his primary tumor and metastatic tumor 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 also be promising biomarkers in ESCC individuals receiving ICIs.
format	article
author	Tian Zeng Lei Zhang Can Chen Xiang Zhao Xiaoqing Liu Fengwei Ran Tingting Yong Ying Yang Henghui Zhang Henghui Zhang Henghui Zhang Yanling Zhang
author_facet	Tian Zeng Lei Zhang Can Chen Xiang Zhao Xiaoqing Liu Fengwei Ran Tingting Yong Ying Yang Henghui Zhang Henghui Zhang Henghui Zhang Yanling Zhang
author_sort	Tian Zeng
title	Durable Complete Response to Pembrolizumab in Esophageal Squamous Cell Carcinoma With Divergent Microsatellite Status: A Case Report
title_short	Durable Complete Response to Pembrolizumab in Esophageal Squamous Cell Carcinoma With Divergent Microsatellite Status: A Case Report
title_full	Durable Complete Response to Pembrolizumab in Esophageal Squamous Cell Carcinoma With Divergent Microsatellite Status: A Case Report
title_fullStr	Durable Complete Response to Pembrolizumab in Esophageal Squamous Cell Carcinoma With Divergent Microsatellite Status: A Case Report
title_full_unstemmed	Durable Complete Response to Pembrolizumab in Esophageal Squamous Cell Carcinoma With Divergent Microsatellite Status: A Case Report
title_sort	durable complete response to pembrolizumab in esophageal squamous cell carcinoma with divergent microsatellite status: a case report
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e2b5abf2a3bf42fe98dacd41ae6af75e
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Durable Complete Response to Pembrolizumab in Esophageal Squamous Cell Carcinoma With Divergent Microsatellite Status: A Case Report

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