AUTHOR=Wang Zifei , Zhong Yu , Zhang Zefan , Zhou Kaiqian , Huang Zhihao , Yu Hao , Liu Longqi , Liu Shiping , Yang Huanming , Zhou Jian , Fan Jia , Wu Liang , Sun Yunfan TITLE=Characteristics and Clinical Significance of T-Cell Receptor Repertoire in Hepatocellular Carcinoma JOURNAL=Frontiers in Immunology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.847263 DOI=10.3389/fimmu.2022.847263 ISSN=1664-3224 ABSTRACT=Several recent studies have demonstrated that the T cell receptor (TCR) repertoire is associated with prognosis and immune therapy response in several types of cancer. The aim of this study is to explore the comprehensive features of the hepatocellular carcinoma (HCC) TCR repertoire, as well as its clinical significance of diagnosis in hepatocellular carcinoma (HCC) patients. Here, we perform high throughput TCR sequencing on paired tumor/ peritumoral tissue and peripheral blood samples from 58 HCC patients to dissect comprehensive TCR features and the clinical significance of peripheral TCR repertoire. By exploring the abundance and diversity of TCR repertoires, we observe there was a significantly higher TCR diversity in peripheral blood than in tumoral and peritumoral tissues, while tumoral and peritumoral tissue showed similar TCR diversity. Substantial difference of the usage frequencies of several Vβ, Jβ genes and TCRβ VJ pairings was found among three types of tissues. Moreover, we reveal that HCC patients have a unique profile of TCR repertoire in peripheral blood in contrast to healthy individuals. We further establish an HCC diagnostic model based on TCRβ VJ pairings usage in peripheral blood, which yields a best-fit area under the curve (AUC) of 0.9746±0.0481 (Sensitivity = 0.9675±0.0603, Specificity = 0.9998±0.0007, average of 100 repeats) in the test set. In general, we comprehensively depict the overall characteristics of tissue-infiltrating and circulating T cell repertoire in HCC patients. Our results suggest that the circulating TCR repertoire might be a promising biomarker for non-invasive diagnosis of HCC patients.