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

ABSTRACT:

Background

The 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.

Methods

By 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.

Results

High 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.

Conclusions

We 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.

SUBMITTER: Xie S

PROVIDER: S-EPMC10258310 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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