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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| http://dx.doi.org/10.1186/s12967-024-05825-0 | DOI Listing |
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