Inverse correlation of HER2 with MHC class I expression on oesophageal squamous cell carcinoma.
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.


CONCLUSIONS
HER2-overexpressing ESCC tumour cells showed a reduced sensitivity for CTLs through the downregulation of MHC class I.
Maruyama
T
T
First Department of Surgery, University of Yamanashi, 1110 Shimokato, Chuo-city, Yamanashi 409-3898, Japan.
Mimura
K
K
Sato
E
E
Watanabe
M
M
Mizukami
Y
Y
Kawaguchi
Y
Y
Ando
T
T
Kinouchi
H
H
Fujii
H
H
Kono
K
K
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005805:Genes, MHC Class I / Q000235:genetics*; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*
D018719:Erb-b2 Receptor Tyrosine Kinases