T cell receptor and B cell receptor exhibit unique signatures in tumor and adjacent non-tumor tissues of hepatocellular carcinoma

Frontiers in Immunology

Immunology

Yu Wang¹  Longqing Tang²  Jiabang Liu³  Mengfen Shi³  Zhanhui Wang³  Yifan Gan³  Xueying Li³  Li Liu³  Shi Xie³  Rong Yan³  Anqi Zheng³  Deke Jiang³  Hongkai Wu⁴ 

[1] Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China;Drug Discovery, HRYZ Biotech Co., Shenzhen, China;Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China;State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China;

关键词: immune repertoire;    immunotherapy;    tumor microenvironment;    T cell receptor;    B cell receptor;    prognosis;   

DOI  :  10.3389/fimmu.2023.1161417

 received in 2023-02-08, accepted in 2023-05-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundThe tumor microenvironment in hepatocellular carcinoma (HCC) is complicated. Tumor-infiltrating T and B cells play a pivotal role in anti-tumor immunity. T cell receptor (TCR) and B cell receptor (BCR) features may reflect the disease-associated antigen response.MethodsBy combining bulk TCR/BCR-sequencing, RNA-sequencing, whole exome-sequencing, and human leukocyte antigen-sequencing, we examined the immune repertoire (IR) features of tumor and adjacent non-tumor tissues obtained from 64 HCC patients.ResultsHigh IR heterogeneity with weak similarity was discovered between tumor and non-tumor tissues. Higher BCR diversity, richness, and somatic hypermutation (SHM) were found in non-tumor tissues, while TCRα and TCRβ diversity and richness were comparable or higher in tumor. Additionally, lower immune infiltration was found in tumor than non-tumor tissues; the microenvironment in tumor appeared to keep stably inhibited and changed slightly with tumor progression. Moreover, BCR SHM was stronger, whereas TCR/BCR diversity declined with HCC progression. Importantly, we found that higher IR evenness in tumor and lower TCR richness in non-tumor tissues indicated better survival in HCC patients. Collectively, the results revealed that TCR and BCR exhibited distinct features in tumor and non-tumor tissues.ConclusionsWe demonstrated that IR features vary between different tissues of HCC. IR features may represent a biomarker for the diagnosis and treatment of HCC patients, providing references for subsequent immunotherapy research and strategy selection.

【 授权许可】

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Copyright © 2023 Xie, Yan, Zheng, Shi, Tang, Li, Liu, Gan, Wang, Jiang, Liu, Wu and Wang