Annexin A3 as a potential target for immunotherapy of liver cancer stem-like cells

Area of Science:

• Oncology
• Immunology
• Cell Biology

Background:

• Cancer stem-like cells (CSCs) drive tumor recurrence and metastasis and resist conventional therapies.
• Identifying CSC-specific targets is crucial for developing effective cancer treatments.
• Hepatocellular carcinoma (HCC) remains a significant global health challenge with limited therapeutic options.

Purpose of the Study:

• To investigate Annexin A3 (ANXA3) as a potential therapeutic target for CSCs/CICs in HCC.
• To establish an immunotherapy strategy targeting ANXA3-expressing CSCs/CICs.

Main Methods:

• Comparative analysis of ANXA3 expression in HCC CSCs/CICs versus non-CSCs/CICs.
• Correlation analysis of ANXA3 and CD133 expression with HCC progression.
• Functional studies involving ANXA3 overexpression and knockdown in HCC cells.
• Mechanistic investigation of the ANXA3 signaling pathway (HIF1A/Notch).
• Development and evaluation of ANXA3-targeted dendritic cell immunotherapy.

Main Results:

• ANXA3 is preferentially expressed in HCC CSCs/CICs and correlates with CD133 expression and HCC progression.
• ANXA3 overexpression enhances CSC/CIC properties and tumorigenicity, while knockdown inhibits them.
• ANXA3 maintains HCC CSC/CIC activity, potentially via the HIF1A/Notch pathway.
• ANXA3-targeted dendritic cell immunotherapy effectively activates T cells to kill HCC CSCs/CICs in vitro and in vivo.

Conclusions:

• ANXA3 plays a critical role in maintaining HCC CSC/CIC populations and their activity.
• ANXA3 represents a promising CSC/CIC-specific therapeutic target for HCC.
• ANXA3-based immunotherapy demonstrates potential for improving HCC treatment outcomes.