Circulating Natural Autoantibodies to HER2-Derived Peptides Performed Antitumor Effects on Oral Squamous Cell...

Area of Science:

• Immunology
• Oncology
• Biochemistry

Background:

• Natural autoantibodies are vital for immune surveillance against malignant tumors.
• Epidermal Growth Factor Receptor 2 (HER2) is overexpressed in various epithelial cancers, including oral squamous cell carcinoma (OSCC).

Purpose of the Study:

• To investigate the therapeutic potential of anti-HER2 natural autoantibodies in oral squamous cell carcinoma (OSCC).

Main Methods:

• HER2 expression analysis in OSCC tissues.
• Quantification of plasma anti-HER2 IgG levels using ELISA.
• In vitro treatment of OSCC cells with anti-HER2 IgG-rich plasma and intravenous immunoglobulin (IVIg).
• Assessment of OSCC cell proliferation, invasion, apoptosis, and epithelial-mesenchymal transition (EMT).
• HER2 gene knockdown using siRNAs to confirm target specificity.

Main Results:

• OSCC tissues exhibit significantly higher HER2 expression compared to adjacent tissues, particularly in advanced stages.
• Distinct differences in plasma anti-HER2 IgG levels were observed between healthy controls, benign oral tumor individuals, and OSCC patients.
• Anti-HER2 IgG and IVIg treatments significantly inhibited OSCC cell proliferation and invasion, induced apoptosis, and modulated apoptosis-associated factors and EMT.
• Complement-dependent cytotoxicity (CDC) pathway involvement was suggested in anti-HER2 IgG-mediated OSCC cell inhibition.
• HER2 gene knockdown abrogated the inhibitory effects of anti-HER2 antibodies on OSCC cells.

Conclusions:

• Human plasma IgG or IVIg targeting HER2 represents a promising therapeutic strategy for anti-OSCC treatment.
• Targeting HER2 with natural autoantibodies offers a potential new avenue for OSCC immunotherapy.