Expression of MHC Class I on breast cancer cells correlates inversely with HER2 expression
| Autor: | Rolf Kiessling, Kousaku Mimura, Ryohei Katoh, Shugo Shiba, Shingo Inoue, Takanori Maruyama, Tomonori Kawasaki, Yoshihiko Kawaguchi, Masayuki Inoue, Shinichiro Izawa, Aniruddha Choudhury, Mitsuaki Watanabe, Hideki Fujii, Ayako Inoue, Koji Kono, Kensuke Shiraishi |
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| Rok vydání: | 2012 |
| Předmět: |
T cell
Ras/MAPK Immunology CD1 Biology medicine.disease MHC Class I breast cancer Breast cancer medicine.anatomical_structure Oncology Downregulation and upregulation HER2 CTL MHC class I Cancer research medicine biology.protein Immunology and Allergy Cytotoxic T cell PTEN Signal transduction skin and connective tissue diseases Research Paper |
| Zdroj: | Oncoimmunology |
| ISSN: | 2162-402X |
| Popis: | HER2 is a promising target for immunotherapeutic interventions with T cell-based approaches since it is amplified and overexpressed in 20-30% of breast cancers. However, several previous studies including ours showed that HER2-overexpressing tumors may escape cytotoxic T lymphocyte-mediated lysis by downregulating MHC Class I and components of the antigen-processing machinery. The aims of the present study were to analyze the relationship between HER2 and MHC Class I expression and to elucidate the mechanisms underlying MHC Class I downregulation in breast cancer. We explored expression of HER2, MHC Class I, PTEN, Ki67, estrogen and progesterone expression in 70 breast cancer patients by immunohistochemistry (IHC) and analyzed their correlation. We also explored the components of the signal transduction pathway that are involved in the regulation of MHC Class I expression using small-interfering RNAs targeting HER2 as well as an inhibitor of HER2 signaling. HER2 expression in breast cancers correlated inversely with MHC Class I expression analyzed by IHC. HER2 depletion by small-interfering RNAs resulted in MHC Class I upregulation. Moreover, MHC Class I expression on breast cancer cell lines was upregulated by PD98059, an inhibitor of mitogen-associated protein kinases, in a dose-dependent manner. Thus, agents that target the MAPK signaling pathway may increase MHC Class I expression in breast cancer cells. |
| Databáze: | OpenAIRE |
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