Simultaneous production of T helper-1-like cytokines and cytolytic activity by tumor-specific T cells in ovarian and breast cancer

Simultaneous production of T helper-1-like cytokines and cytolytic activity by tumor-specific T cells in ovarian and breast cancer
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DOI:
10.1006/cimm.1996.1055
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发表时间:
1997-02-01
影响因子:
4.3
通讯作者:
Eberlein, TJ
Eberlein, TJ
中科院分区:
医学4区
文献类型:
--
作者:
Goedegebuure, PS;Douville, CC;Eberlein, TJ

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Cytotoxic T-cell (CTL) cultures were generated from five ovarian cancer patients (OvCTL) and from three breast cancer patients (BrCTL). All CTL lines were T-cell receptor (TcR) alpha beta(+) and predominantly CD8(+) (73 +/- 13%). These CTL lines preferentially recognized autologous tumor cells in an HLA class I-restricted, and in part HLA-A2-restricted, manner. In addition, the CTL lines recognized allogeneic HLA-A2(+) ovarian and breast tumor cells. Specific recognition was determined by T-cell-mediated cytotoxicity as well as cytokine release. Coculture of irradiated autologous tumor cells with OvCTL induced secretion of IFN-gamma, GM-CSF and TNF-alpha, but not IL-4, indicating a T helper-1-type response. Similar results were obtained when OvCTL and BrCTL were stimulated with histologically matched HLA-A2(+) tumor cells. Also, BrCTL stimulated with HLA-A2(+) but not HLA-A2(-) ovarian tumor cells produced significant levels of GM-CSF and TNF-alpha. Finally, the Her2/neu peptide p654-662, earlier identified as a tumor antigen in both ovarian and breast cancer, induced cytotoxicity as well as the specific release of IFN-gamma and TNF-alpha but not IL-4 by OvCTL and BrCTL. Thus, tumor-specific recognition by CTL was verified by cytotoxicity and cytokine release. The secretion of Th1-like cytokines as opposed to Th2-like cytokines suggest that therapeutically OvCTL and BrCTL could potentially enhance the endogenous immune response to tumor. (C) 1997 Academic Press.