Expression of MHC Class I on breast cancer cells correlates inversely with HER2 expression

被引：61

作者：

Inoue, Masayuki ^{[1
]}

Mimura, Kousaku ^{[1
,2
]}

Izawa, Shinichiro ^{[1
]}

Shiraishi, Kensuke ^{[1
]}

Inoue, Ayako ^{[1
]}

Shiba, Shugo ^{[1
]}

Watanabe, Mitsuaki ^{[1
]}

Maruyama, Takanori ^{[1
]}

Kawaguchi, Yoshihiko ^{[1
]}

Inoue, Shingo ^{[1
]}

Kawasaki, Tomonori ^{[3
]}

Choudhury, Aniruddha ^{[4
]}

Katoh, Ryohei ^{[3
]}

Fujii, Hideki ^{[1
]}

Kiessling, Rolf ^{[5
]}

Kono, Koji ^{[1
,2
,6
]}

机构：

[1] Univ Yamanashi, Dept Surg 1, Yamanashi, Japan

[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Surg, Singapore 117595, Singapore

[3] Univ Yamanashi, Dept Pathol, Yamanashi, Japan

[4] Univ Queensland, Ctr Immune & Targeted Therapy, Greenslopes Private Hosp, Greenslopes, Australia

[5] Karolinska Hosp, Dept Oncol & Pathol, Immune & Gene Therapy Lab, Canc Ctr Karolinska, S-10401 Stockholm, Sweden

[6] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore

来源：

ONCOIMMUNOLOGY | 2012年 / 1卷 / 07期

关键词：

MHC Class I; HER2; breast cancer; Ras/MAPK; CTL; CYTOTOXIC T-LYMPHOCYTES; GROUP-STUDY I-01; HLA CLASS-I; CLINICAL-TRIAL; E75; VACCINE; DOWN-REGULATION; HER-2/NEU; CARCINOMA; TUMOR; PEPTIDE;

D O I：

10.4161/onci.21056

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 MAP K signaling pathway may increase MHC Class I expression in breast cancer cells.

引用

页码：1104 / 1110

页数：7

共 34 条

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