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Multiomics Analysis of Interleukin-21 as a Potential Immunologic and Biomarker in Hepatocellular Carcinoma
Yonghui Ma1, Guanming Shao, Yuwei Xie
1Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Abstract:
Interleukin-21 (IL-21) is an important antitumor cytokine that contributes to the proliferation and differentiation of CD8 + T cells. It has been proven to enhance the response to immune checkpoint inhibitors (ICIs) in various solid tumors. However, its role in hepatocellular carcinoma (HCC) has not yet been clarified. In this research, we aimed to investigate the antitumor effect of IL-21 in HCC and its effect on ICI treatment. Through transcriptome sequencing analysis and immunohistochemistry validation, we found that patients with high IL-21 expression had a better prognosis. HCCs with high expression of IL-21 had higher infiltration of CD8 + T cells, increased expression of immune checkpoints, and an improved response to ICI treatment. In conclusion, IL-21 can enhance the efficacy of ICI treatment and improve the prognosis of patients by promoting the infiltration of CD8 + T cells and the expression of immune checkpoint-related genes.
Insights
High Interleukin-21 (IL-21) expression in hepatocellular carcinoma (HCC) correlates with better patient prognosis and improved response to immune checkpoint inhibitors (ICIs). IL-21 promotes CD8+ T cell infiltration, enhancing antitumor immunity.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Interleukin-21 (IL-21) is a cytokine known for its antitumor properties, enhancing CD8+ T cell responses.
- IL-21 has shown efficacy in improving immune checkpoint inhibitor (ICI) treatment outcomes in several solid tumors.
- The specific role of IL-21 in hepatocellular carcinoma (HCC) and its impact on ICI therapy remains unclear.
Purpose of the Study:
- To investigate the antitumor effects of IL-21 in HCC.
- To determine the influence of IL-21 on the efficacy of ICI treatment in HCC patients.
Main Methods:
- Transcriptome sequencing analysis was employed to assess gene expression profiles.
- Immunohistochemistry was used for validation of key findings.
- Correlation between IL-21 expression, immune cell infiltration, and clinical outcomes was analyzed.
Main Results:
- Higher IL-21 expression was associated with a better prognosis in HCC patients.
- HCC tumors with high IL-21 expression exhibited increased infiltration of CD8+ T cells.
- Elevated IL-21 levels correlated with increased expression of immune checkpoints and enhanced response to ICI treatment.
Conclusions:
- IL-21 demonstrates significant antitumor effects in HCC.
- IL-21 enhances ICI treatment efficacy by promoting CD8+ T cell infiltration and immune checkpoint gene expression.
- IL-21 represents a potential therapeutic target for improving HCC patient outcomes.
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