Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor.
Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor.
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DOI：
10.1172/jci16492
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发表时间：
2003-03
期刊：
影响因子：
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通讯作者：
Li Yang;N. Yamagata;Rajwardhan Yadav;S. Brandon;R. Courtney;J. Morrow;Y. Shyr;M. Boothby;S. Joyce;D. Carbone;R. Breyer
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文献类型：
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作者：
Li Yang;N. Yamagata;Rajwardhan Yadav;S. Brandon;R. Courtney;J. Morrow;Y. Shyr;M. Boothby;S. Joyce;D. Carbone;R. Breyer
前列腺素E(2) （PGE(2)）是COX的主要代谢物，在肿瘤生物学的几个方面起着重要作用。我们利用EP2（-/-）小鼠表征了PGE(2) EP2受体在癌症相关免疫缺陷中的作用。与野生型小鼠相比，EP2（-/-）小鼠在MC26或Lewis肺癌细胞系刺激下，肿瘤生长明显减弱，存活时间更长。虽然没有观察到T细胞功能的差异，但PGE(2)抑制了野生型骨髓祖细胞的dc分化，而ep2缺失细胞则难以受到这种影响。PGE抑制了野生型dc对混合淋巴细胞反应中细胞的刺激(2)，而EP2（-/-）来源的dc对这种作用有抵抗性。在体内实验中，与野生型小鼠相比，携带肿瘤的EP2（-/-）小鼠引流淋巴结中的dc、CD4（+）和CD8(+) T细胞明显丰富，并且仅在携带肿瘤的EP2（-/-）小鼠中可以观察到显著的抗肿瘤细胞毒性T细胞反应。我们的数据表明，EP2受体在PGE(2)诱导的DC分化和功能抑制以及体内抗肿瘤细胞免疫反应减弱中发挥重要作用。
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.