The intratumoral landscape of T cell receptor repertoire in esophageal squamous cell carcinoma

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a malignant neoplasm with detrimental implications for human health. The landscape of ESCC therapy has been revolutionized by the introduction of immunotherapy, specifically involving immune checkpoint inhibitors (ICIs). A number of st...

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Main Authors: Meng Yang, Dan He, Yu Sun, Yunquan Guo, Yu Ma, Lin Feng, Meng Liu
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Journal of Translational Medicine
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Online Access:https://doi.org/10.1186/s12967-024-05825-0
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author Meng Yang
Dan He
Yu Sun
Yunquan Guo
Yu Ma
Lin Feng
Meng Liu
author_facet Meng Yang
Dan He
Yu Sun
Yunquan Guo
Yu Ma
Lin Feng
Meng Liu
author_sort Meng Yang
collection DOAJ
description Abstract Background Esophageal squamous cell carcinoma (ESCC) is a malignant neoplasm with detrimental implications for human health. The landscape of ESCC therapy has been revolutionized by the introduction of immunotherapy, specifically involving immune checkpoint inhibitors (ICIs). A number of studies have documented the prognostic significance of T-cell receptor (TCR) repertoire and its association with many tumors. Nevertheless, the TCR repertoire landscape and its significance in ESCC still need to be explored. Methods In this study, we conducted RNA-Seq analysis to investigate the characteristics of the TCR repertoire in 90 patients. Moreover, high-throughput TCR sequencing was performed on tumor tissues from 41 patients who received immunotherapy. Additionally, a comprehensive analysis of the T-cell receptor repertoire landscape within ESCC tumors was carried out through immunohistochemical staining on all patient samples. Results We noticed a diminished diversity of TCR repertoire within the tumor compared to its adjacent normal tissue. In terms of immunotherapy responses, non-responsive patients exhibited higher TCR repertoire diversity indices and an increased frequency of common V and J genes. Additionally, elevated TCR repertoire diversity correlated with improved overall survival rates. Lastly, immunohistochemical staining results indicated a correlation between TCR repertoire diversity and the tumor immune microenvironment (TIME). Conclusions Our study primarily describes the landscape of TCR repertoires in ESCC through three aspects: differences in tumor tissues, immune response to immunotherapy, and survival prognosis of patients. These results emphasize the importance of TCR repertoire characteristics as unique and relevant biomarkers for ESCC immunotherapy.
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spelling doaj-art-cbff68607cde4c7eb4022dd69fc6cb512025-08-20T02:51:18ZengBMCJournal of Translational Medicine1479-58762024-11-0122111310.1186/s12967-024-05825-0The intratumoral landscape of T cell receptor repertoire in esophageal squamous cell carcinomaMeng Yang0Dan He1Yu Sun2Yunquan Guo3Yu Ma4Lin Feng5Meng Liu6Affiliated Tumor Hospital of Xinjiang Medical UniversityAffiliated Tumor Hospital of Xinjiang Medical UniversityState Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences, Peking Union Medical CollegeAffiliated Tumor Hospital of Xinjiang Medical UniversityThe Fourth People’ Hospital of Urumqi, Xinjiang Uygur Autonomous RegionState Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences, Peking Union Medical CollegeAffiliated Tumor Hospital of Xinjiang Medical UniversityAbstract Background Esophageal squamous cell carcinoma (ESCC) is a malignant neoplasm with detrimental implications for human health. The landscape of ESCC therapy has been revolutionized by the introduction of immunotherapy, specifically involving immune checkpoint inhibitors (ICIs). A number of studies have documented the prognostic significance of T-cell receptor (TCR) repertoire and its association with many tumors. Nevertheless, the TCR repertoire landscape and its significance in ESCC still need to be explored. Methods In this study, we conducted RNA-Seq analysis to investigate the characteristics of the TCR repertoire in 90 patients. Moreover, high-throughput TCR sequencing was performed on tumor tissues from 41 patients who received immunotherapy. Additionally, a comprehensive analysis of the T-cell receptor repertoire landscape within ESCC tumors was carried out through immunohistochemical staining on all patient samples. Results We noticed a diminished diversity of TCR repertoire within the tumor compared to its adjacent normal tissue. In terms of immunotherapy responses, non-responsive patients exhibited higher TCR repertoire diversity indices and an increased frequency of common V and J genes. Additionally, elevated TCR repertoire diversity correlated with improved overall survival rates. Lastly, immunohistochemical staining results indicated a correlation between TCR repertoire diversity and the tumor immune microenvironment (TIME). Conclusions Our study primarily describes the landscape of TCR repertoires in ESCC through three aspects: differences in tumor tissues, immune response to immunotherapy, and survival prognosis of patients. These results emphasize the importance of TCR repertoire characteristics as unique and relevant biomarkers for ESCC immunotherapy.https://doi.org/10.1186/s12967-024-05825-0T cell receptor repertoireImmunotherapy responseEsophageal squamous cell carcinomaOverall survival
spellingShingle Meng Yang
Dan He
Yu Sun
Yunquan Guo
Yu Ma
Lin Feng
Meng Liu
The intratumoral landscape of T cell receptor repertoire in esophageal squamous cell carcinoma
Journal of Translational Medicine
T cell receptor repertoire
Immunotherapy response
Esophageal squamous cell carcinoma
Overall survival
title The intratumoral landscape of T cell receptor repertoire in esophageal squamous cell carcinoma
title_full The intratumoral landscape of T cell receptor repertoire in esophageal squamous cell carcinoma
title_fullStr The intratumoral landscape of T cell receptor repertoire in esophageal squamous cell carcinoma
title_full_unstemmed The intratumoral landscape of T cell receptor repertoire in esophageal squamous cell carcinoma
title_short The intratumoral landscape of T cell receptor repertoire in esophageal squamous cell carcinoma
title_sort intratumoral landscape of t cell receptor repertoire in esophageal squamous cell carcinoma
topic T cell receptor repertoire
Immunotherapy response
Esophageal squamous cell carcinoma
Overall survival
url https://doi.org/10.1186/s12967-024-05825-0
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