title: Expression of MHC Class I on breast cancer cells correlates inversely with HER2 expression.
abstract: 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.
authors.affiliation: First Department of Surgery; University of Yamanashi; Yamanashi, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Inoue
authors.forename: Kousaku
authors.initials: K
authors.lastname: Mimura
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Izawa
authors.forename: Kensuke
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Ayako
authors.initials: A
authors.lastname: Inoue
authors.forename: Shugo
authors.initials: S
authors.lastname: Shiba
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Takanori
authors.initials: T
authors.lastname: Maruyama
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Shingo
authors.initials: S
authors.lastname: Inoue
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Aniruddha
authors.initials: A
authors.lastname: Choudhury
authors.forename: Ryohei
authors.initials: R
authors.lastname: Katoh
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Rolf
authors.initials: R
authors.lastname: Kiessling
authors.forename: Koji
authors.initials: K
authors.lastname: Kono