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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.767957/full |
| _version_ | 1828956521110700032 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T08:12:49Z |
| format | Article |
| id | doaj.art-e2b5abf2a3bf42fe98dacd41ae6af75e |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-14T08:12:49Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e2b5abf2a3bf42fe98dacd41ae6af75e2022-12-21T23:10:02ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-11-011110.3389/fonc.2021.767957767957Durable Complete Response to Pembrolizumab in Esophageal Squamous Cell Carcinoma With Divergent Microsatellite Status: A Case ReportTian Zeng0Lei Zhang1Can Chen2Xiang Zhao3Xiaoqing Liu4Fengwei Ran5Tingting Yong6Ying Yang7Henghui Zhang8Henghui Zhang9Henghui Zhang10Yanling Zhang11Department of Oncology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaGenecast Biotechnology Co., Ltd., Wuxi, ChinaDepartment of Oncology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Oncology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Oncology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Oncology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Oncology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaGenecast Biotechnology Co., Ltd., Wuxi, ChinaBeijing Shijitan Hospital, Capital Medical University, Beijing, ChinaNinth School of Clinical Medicine, Peking University, Beijing, ChinaSchool of Oncology, Capital Medical University, Beijing, ChinaDepartment of Oncology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaMicrosatellite 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.767957/fullesophageal squamous cell carcinomamicrosatellite instabilitypembrolizumabcomplete responseDNA damage repair |
| spellingShingle | 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 Frontiers in Oncology esophageal squamous cell carcinoma microsatellite instability pembrolizumab complete response DNA damage repair |
| title | 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_short | 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 |
| topic | esophageal squamous cell carcinoma microsatellite instability pembrolizumab complete response DNA damage repair |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.767957/full |
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