Assessing the chronic hepatitis B adaptive immune response by profiling specific T-cell receptor repertoire.

Challenges in assessing hepatitis B virus (HBV)-specific T cell immunity as an immunological biomarker still remain in chronic hepatitis B (CHB), such as the requirement of large quantities of cells. This study aims to conveniently assess HBV-specific T cells immunity in chronic HBV infected patients. We obtained T cell receptor ß chains (TCRßs) from public databases and six acute hepatitis B patients to establish an HBV-specific TCRßs dataset. For some TCRs from one acute patient, their specificities and epitopes were verified. The potential HBV-specific TCRßs from CHB patients were analyzed using GLIPH2 and established dataset. By analyzing two antiviral therapy cohorts including 42 CHB patients, we showed that individuals with better therapy response may depend more on newly emerging potential HBV-specific TCRßs. In a cross-sectional study containing 207 chronic HBV infected patients, the results exhibited that the characteristics of potential HBV-specific clusters were divergent between CHB and hepatocellular carcinoma patients. Our strategy could profile potential HBV-specific TCRß repertoire using a small blood sample, which will complement traditional methods for assessing the HBV-specific T cell immunity.

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

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 TCRß 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.