Effective T-Cell Receptor Profiles Predict Survival in HCC

Introduction to Hepatocellular Carcinoma and TCR Importance

Hepatocellular carcinoma (HCC) represents one of the most prevalent malignancies globally, significantly contributing to cancer-related mortality. The complexity of HCC arises primarily from its association with chronic liver diseases such as hepatitis B and C, cirrhosis, and fatty liver disease. According to recent statistics, HCC accounts for approximately 90% of primary liver cancer cases, with over 800,000 deaths annually (McGlynn et al., 2021). While surgical resection remains the gold standard for curative treatment, the prognosis for patients with advanced stages of the disease is often dismal, with a 5-year survival rate of less than 20% for those diagnosed at later stages (Gao et al., 2016).

The immune microenvironment of tumors, particularly the composition and diversity of T-cell receptor (TCR) profiles, plays a crucial role in the prognosis and treatment response of HCC patients. Tumor-infiltrating lymphocytes (TILs), particularly CD8+ T cells, are critical for anti-tumor immunity and have been linked to improved survival outcomes in various cancers, including HCC (Kristensen et al., 2017). Characterizing TCR profiles can provide insights into the adaptive immune response against tumors, guiding treatment strategies and enhancing the efficacy of immunotherapies.

Study Objectives: Assessing Efficacy of CGD Treatment

This study aims to evaluate the potential of TCR repertoire characterization as a prognostic biomarker for HCC, with a focus on understanding how specific TCR profiles correlate with survival outcomes in patients. By analyzing TCR diversity and composition through high-throughput sequencing, the study seeks to establish a correlation between TCR profiles and clinical outcomes, including overall survival (OS) and progression-free survival (PFS). The insights gained from this research could significantly impact the management of HCC by identifying patients who may benefit from immunotherapy.

Methodology: Patient Selection and Data Analysis Techniques

The study involved a retrospective cohort of HCC patients who underwent surgical resection at a single institution. Patients were classified into two groups based on survival time: long-survivors (LS) and short-survivors (SS). The LS group consisted of patients who survived for at least 24 months post-diagnosis, while the SS group included those who succumbed to the disease within 12 months.

High-throughput sequencing technology was employed to analyze the TCR β-chain repertoires from tumor tissues of 31 patients. The diversity of TCR repertoires was assessed using indices such as Shannon and Simpson diversity indexes. Additionally, principal component analysis (PCA) was conducted to visualize the differences in TCR profiles between the LS and SS groups. Statistical analyses were performed to identify significant associations between specific TCR gene segments and survival outcomes.

Table 1: Patient Characteristics

Results: TCR Diversity and Its Relationship with Survival Rates

The findings revealed that the TCR compositions in long-survivors were less diverse compared to short-survivors. Notably, specific TCR gene segments such as TRBJ1-3, TRBV10-1, TRBV15, and TRBV6-5 showed significantly higher usage in the LS group, while TRBJ2-2 was less prevalent. The PCA analysis illustrated clear discrimination between the two groups based on TCR profiles, indicating that TCR diversity may serve as a significant prognostic marker in HCC.

Additionally, differential usage of CDR3 sequences between LS and SS patients was observed, with five CDR3 sequences upregulated in the LS group. These findings suggest a potential link between specific TCR profiles and improved survival outcomes, underscoring the importance of TCR repertoire analysis in understanding tumor immunity and guiding therapeutic strategies.

Table 2: Differential TCR Gene Segment Usage

Conclusion: Implications of TCR Characterization for HCC Treatment

The present study contributes to the understanding of TCR profiles in HCC and their potential role as prognostic biomarkers. The differential TCR profiles observed between long-survivors and short-survivors highlight the importance of T cell immunity in HCC prognosis. These findings suggest that TCR repertoire analysis could be integrated into clinical practice to stratify patients based on expected outcomes and tailor individualized immunotherapy approaches.

As the efficacy of immunotherapy continues to evolve, understanding the relationship between TCR profiles and patient outcomes will be essential for optimizing treatment strategies in HCC. Future studies should aim to validate these findings in larger cohorts and explore the underlying mechanisms linking TCR diversity to tumor immunity.

FAQ

What is hepatocellular carcinoma (HCC)?
HCC is the most common type of primary liver cancer, often associated with chronic liver diseases such as hepatitis B and C, cirrhosis, and fatty liver disease.

Why are T cell receptor (TCR) profiles important for HCC patients?
TCR profiles can reflect the immune response against tumors and may help in predicting survival outcomes, guiding treatment strategies such as immunotherapy.

How was the TCR diversity measured in the study?
TCR diversity was assessed using high-throughput sequencing technology, with diversity indices such as Shannon and Simpson used to quantify TCR repertoire characteristics.

What were the main findings regarding TCR profiles in HCC patients?
The study found that long-survivors had less diverse TCR profiles compared to short-survivors, with specific TCR gene segments being more prevalent in long-survivors.

What are the implications of these findings for HCC treatment?
Understanding TCR profiles could assist in stratifying HCC patients for better prognostic assessments and more tailored immunotherapy approaches.

References

1. McGlynn, K. A., Petrick, J. L., & El-Serag, H. B. (2021). Epidemiology of hepatocellular carcinoma. Hepatology, 73(Suppl 1), 4-13
2. Gao, J., Xiong, Y., Wang, Y., Wang, Y., & Zheng, G. (2016). Hepatitis B virus X protein activates notch signaling by its effects on Notch1 and Notch4 in human hepatocellular carcinoma. International Journal of Oncology, 48(1), 329-337
3. Kristensen, V. N., et al. (2017). The antigenicity of the tumor cell - context matters. New England Journal of Medicine, 376(5), 491-493
4. Han, Y., Liu, X., Wang, Y., et al. (2015). Identification of characteristic TRB V usage in HBV-associated HCC by using differential expression profiling analysis. Oncoimmunology, 4(8), e1021537
5. Zhuang, Y., Zhang, C., Wu, Q., Zhang, J., Ye, Z., & Qian, Q. (2019). Application of immune repertoire sequencing in cancer immunotherapy. International Immunopharmacology, 74, 105688. https://doi.org/10.1016/j.intimp.2019.105688
6. Yang, J., Xu, S. Y., Xiao, D. S., Li, J. Y., Jin, X. Y., & Yan, D. (2024). Similar usage of T-cell receptor β-chain between tumor and adjacent normal tissue in hepatocellular carcinoma. Cancer Medicine, 13(16), e70121
7. Ruiz, M., Giudicelli, V., Ginestoux, C., et al. (2000). IMGT, the international ImMunoGeneTics database. Nucleic Acids Research, 28(1), 219-221
8. McShane, L. M., Altman, D. G., Sauerbrei, W., Taube, S. E., Gion, M., & Clark, G. M. (2005). REporting recommendations for tumour MARKer prognostic studies (REMARK). British Journal of Cancer, 93(4), 387-391. https://doi.org/10.1038/sj.bjc.6602678
9. Wang, F., et al. (2025). Characterization of T-Cell Receptor Profiles Predicts Survival Situation in Patients with Hepatocellular Carcinoma. Technology in Cancer Research & Treatment, 23, 15330338251329699