T cell dysfunction in chronic hepatitis B infection and liver cancer: evidence from transcriptome analysis

Abstract

BackgroundT cell dysfunction occurs in many diseases, especially in chronic virus infection and cancers. However, up to now, little is known on the distinctions in T cell exhaustion between cancer and chronic virus infection. The objective of this study is to explore the transcriptional similarities and differences in exhausted CD8 +T cell between chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC).MethodsRNA sequencing was performed to compare the transcriptome of CD8 +T cells isolated from healthy donors’ blood, tumour tissues of patients with HCC and chronic HBV infected HCC patients’ paracancerous tissues. DESeq2 algorithm was used to determine differentially expressed genes. Gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted for in-depth analysis of these differentially expressed genes.ResultsA total number of 2109 and 2203 genes were differentially expressed in patients with chronic HBV infection and HCC, respectively. Comparing these two groups of differentially deregulated genes, we found that nearly half of them were shared, and these shared genes were further classified into several functional categories, such as metabolic process, binding and intracellular organelle. KEGG analysis revealed that these shared deregulated genes were involved in many important pathways such as Parkinson’s disease, oxidative phosphorylation and messenger RNA surveillance. Interestingly, we reported that chronic HBV infection specific deregulated genes were mainly enriched in graft versus host disease, allograft rejection, phenylalanine, tyrosine and tryptophan biosynthesis pathways. Whereas, HCC-specific deregulated genes were highly enriched in oxidative phosphorylation, thyroid cancer and endometrial cancer pathways.ConclusionOur study demonstrated that T cell dysfunction associated with HCC and chronic HBV infection shares high similarities, however, each possesses its own features in terms of specific genes and signalling pathways. Uncovering the differences of T cells dysfunction would facilitate our understanding the diseases pathogenesis and developing innovative therapies in the future.

Thymoma Associated Myasthenia Gravis (TAMG): Differential Expression of Functional Pathways in Relation to MG Status in Different Thymoma Histotypes

“…Furthermore, expression of the brain-type ryanodine receptor, RYR3, in thymomas has been shown to be associated with TAMG (8), but in this case we now find that the association is strongest in type B2 thymomas (Figure S2). Of note, pathways that play a role in the above mentioned neurodegenerative diseases, have been found enriched in a variety of immunobiological settings, including chronic infections, graft-vs.-host disease, cancer biology, cell death, and inflammation (15)(16)(17). Likewise, the "Adherens junction" pathway that was the most significantly downregulated TAMG-associated pathway in type AB thymomas ( Table 1) has been linked to thymic hypoplasia and lymphopenia (18) and to various autoimmune diseases in conjunction with the leakiness of several blood-tissue and inter-epithelial barriers (19,20).…”

Association of Hepatitis B Virus DNA Level and Follow-up Interval With Hepatocellular Carcinoma Recurrence

“…Although F30V hampers HBV replication, the variation may be associated with hepatocyte survival, potentially allowing persistent production of viral progeny and initiating HBV-driven hepatocarcinogenesis . T-cell dysfunction is associated with chronic HBV infection and HCC, possibly through the mechanism of chronic HBV infection–specific deregulated genes regulating T-cell function . Hepatitis B virus reactivation, irregular antiviral treatment, or overdue drug adjustment after resistance development are associated with OS.…”

“…29 T-cell dysfunction is associated with chronic HBV infection and HCC, possibly through the mechanism of chronic HBV infection-specific deregulated genes regulating T-cell function. 30 Hepatitis B virus reactivation, irregular antiviral treatment, or overdue drug adjustment after resistance development are associated with OS. Possible mechanisms of the benefits of antiviral treatment in HCC management include reducing the risk of HBV reactivation and liver function damage, decreasing mortality associated with hepatic failure, ameliorating HBV-induced hepatitis, and promoting the recovery of rescued liver tissue, which provide more chances for patients to receive local and systemic treatment during recurrence, prolonging OS.…”

Advances in Multi-Omics Applications in HBV-Associated Hepatocellular Carcinoma

“…The HBV transcriptomes of the HCC cells can be used for individualized immunotherapy with engineered T cells and as a treatment measure for a wider range of HBV-associated HCC patients ( 93 ). The transcriptome similarities and differences in CD8 + T cell dysfunction were explored in both chronic HBV infection and HCC patients through high-throughput RNA-seq, and the results demonstrated that CD8 + T cell dysfunction in the two groups shared high similar characteristics, but each had its own characteristics in specific genes and signal pathways ( 94 ).…”