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Updated: Jun 11, 2026
Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
Published on: October 25, 2011
Inverse correlation of HER2 with MHC class I expression on oesophageal squamous cell carcinoma
1First Department of Surgery, University of Yamanashi, 1110 Shimokato, Chuo-city, Yamanashi 409-3898, Japan.
Background:
As HER2 is expressed in 30% of oesophageal squamous cell carcinomas (ESCCs), T-cell-based immunotherapy and monoclonal antibodies targeted against HER2 are attractive, novel approaches for ESCCs. However, it was shown that there is an inverse correlation between HER2 and MHC class I expression on tumours. Thus, the correlation between HER2 and MHC class I expressions on ESCC was evaluated.
Methods:
Expressions of MHC class I and HER2 in ESCC tissues (n=80) and cell lines were assessed by immunohistochemistry, fluorescence in situ hybridisation (FISH), and flow cytometry. We investigated whether HER2 downregulation with small interfering RNA (siRNA) in ESCC cell lines could upregulate the expression of MHC class I and the antigen presentation machinery components, and could increase their sensitivity for tumour antigen-specific CTLs.
Results:
There was an inverse correlation between HER2 and MHC class I expressions in both tumour tissues and cell lines. Downregulation of HER2 with siRNA resulted in the upregulation of MHC class I expression, leading to increased CTL recognition by tumour antigen-specific CTLs.
Conclusion:
HER2-overexpressing ESCC tumour cells showed a reduced sensitivity for CTLs through the downregulation of MHC class I.
Insights
HER2 expression in oesophageal squamous cell carcinoma (ESCC) inversely correlates with MHC class I, reducing cancer cell sensitivity to T-cell attacks. HER2 downregulation boosts MHC class I, enhancing T-cell recognition and potential immunotherapy effectiveness.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- HER2 is expressed in 30% of oesophageal squamous cell carcinomas (ESCC).
- HER2-targeted therapies and T-cell immunotherapy are promising for ESCC.
- An inverse correlation exists between HER2 and MHC class I expression in tumors.
Purpose of the Study:
- To evaluate the correlation between HER2 and MHC class I expression in ESCC.
- To investigate if HER2 downregulation affects MHC class I expression and T-cell sensitivity.
Main Methods:
- Immunohistochemistry, FISH, and flow cytometry assessed HER2 and MHC class I in ESCC tissues and cell lines.
- HER2 was downregulated using small interfering RNA (siRNA) in ESCC cell lines.
- Tumor antigen-specific cytotoxic T-lymphocyte (CTL) sensitivity was evaluated.
Main Results:
- An inverse correlation between HER2 and MHC class I was confirmed in ESCC tissues and cell lines.
- HER2 downregulation via siRNA led to increased MHC class I expression.
- This upregulation enhanced recognition by tumor antigen-specific CTLs.
Conclusions:
- HER2-overexpressing ESCC cells exhibit reduced sensitivity to CTLs due to lower MHC class I expression.
- Targeting HER2 may restore MHC class I expression and improve T-cell-mediated anti-tumor immunity in ESCC.
