期刊
CANCER RESEARCH
卷 67, 期 5, 页码 2265-2273出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-06-2098
关键词
-
类别
The T-cell-mediated antitumor immune response is frequently repressed in the tumor environment by an immunologic barrier, the predominant mediators of which are thought to be interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). We explored the effect of these cytokines on the individual T-cell effector functions on antigen engagement during an antitumor cell attack. Isolated CD4(+) and CD8(+) T cells were antigen-specifically redirected toward carcinoembryonic antigen (CEA)-positive tumor cells by expression of a recombinant T-cell receptor (immunoreceptor), which triggers T-cell activation via CD3 zeta on binding to CEA. Immunoreceptor-activated T cells secrete IFN-gamma, proliferate, and lyse CEA(+) but not CEA(-) tumor cells. Whereas IL-10 has no direct effect on immunoreceptor-triggered effector functions, TGF-beta represses proliferation of both CD4(+) and CD8(+) T cells but neither IFN-gamma secretion nor specific cytolytic activities. CD28 costimulation, however, overcomes TGF-beta-mediated repression in T-cell proliferation. Consequently, T cells redirected by a combined CD28-CD3 zeta signaling immunoreceptor are largely resistant to TGF-beta-mediated repression. This is reflected in vivo by a more pronounced antitumor activity of T cells against TGF-beta-secreting tumors when redirected by a costimulatory CD28-CD3 zeta than by a CD3 zeta signaling immunoreceptor.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据