Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor

被引:195
作者
Yang, L
Yamagata, N
Yadav, R
Brandon, S
Courtney, RL
Morrow, JD
Shyr, Y
Boothby, M
Joyce, S
Carbone, DP
Breyer, RM
机构
[1] Vanderbilt Univ, Sch Med, Dept Med, Div Nephrol, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA
[5] Vanderbilt Univ, Sch Med, Dept Preventat Med, Nashville, TN 37232 USA
关键词
D O I
10.1172/JCI200316492
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Prostaglandin E-2 (PGE(2)), a major COX metabolite, plays important roles in several facets of tumor biology. We characterized the contribution of the PGE(2) EP2 receptor to cancer-associated immune deficiency using EP2(-/-) mice. EP2(-/-) mice exhibited significantly attenuated tumor growth and longer survival times when challenged with MC26 or Lewis lung carcinoma cell lines as compared with their wild-type littermates. While no differences in T cell function were observed, PGE(2) suppressed differentiation of DCs from wild-type bone marrow progenitors, whereas EP2-null cells were refractory to this effect. Stimulation of cells in mixed lymphocyte reactions by wild-type DCs was suppressed by treatment with PGE(2), while EP2(-/-)-derived DCs were resistant to this effect. In vivo, DCs, CD4(+), and CD8(+) T cells were significantly more abundant in draining lymph nodes of tumor-bearing EP2(-/-) mice than in tumor-bearing wild-type mice, and a significant antitumor cytotoxic T lymphocyte response could be observed only in the EP2(-/-) animals. Our data demonstrate an important role for the EP2 receptor in PGE(2)-induced inhibition of DC differentiation and function and the diminished antitumor cellular immune responses in vivo.
引用
收藏
页码:727 / 735
页数:9
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