2004年10月
Anti-HER-2/neu immune responses are induced before the development of clinical tumors but declined following tumorigenesis in HER-2/neu transgenic mice
CANCER RESEARCH
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- 巻
- 64
- 号
- 20
- 開始ページ
- 7588
- 終了ページ
- 7595
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1158/0008-5472.CAN-04-1081
- 出版者・発行元
- AMER ASSOC CANCER RESEARCH
HER-2/neu oncogene products have been implicated as a potential target of T cell-mediated immune responses to HER-2/neu-induced tumors. Using HER-2/neu transgenic mice (oncomice), we investigated whether, and if so how, anti-HER-2/neu immune responses are induced and modulated in these oncomice from birth to tumor initiation. Female oncomice carrying the activated HER-2/neu oncogene displayed apparent hyperplasia in mammary glands at 10 weeks of age and developed mammary carcinomas around an average age of 26 weeks. Unfractionated spleen cells from 10- to 15-week-old oncomice that were cultured without any exogenous stimuli exhibited cytotoxicity against the F31 tumor cell line established from an HER-2/neu-induced mammary carcinoma mass. The final antitumor effectors were a macrophage lineage of cells. However, this effector population was activated, depending on the stimulation of oncomouse CD4(+) T cells with oncomouse-derived antigen-presenting cell (APC) alone or with wild-type mouse APC in the presence of F31 membrane fractions, suggesting the presence of HER-2/neu-primed CD4(+) T cells and HER-2/neu-presenting APC in 10- to 15-week-old oncomice. These antitumor cytotoxic responses were detected at similar to5 weeks of age and peaked at age 10 to 15 weeks. However, the responses then declined at tumor-bearing stages in which the expression of target proteins could progressively increase. This resulted from the dysfunction of CD4(+) T cells but not of APC or effector macrophages. These results indicate that an anti-HER-2/neu CD4(+) T cell-mediated immune response was generated at the pretumorigenic stage but did not prevent tumorigenesis and declined after the development of clinical tumors.
- リンク情報
- ID情報
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- DOI : 10.1158/0008-5472.CAN-04-1081
- ISSN : 0008-5472
- Web of Science ID : WOS:000224522200057