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

Yang L, Yamagata N, Yadav R, Brandon S, Courtney RL, Morrow JD, Shyr Y, Boothby M, Joyce S, Carbone DP, Breyer RM
J Clin Invest. 2003 111 (5): 727-35

PMID: 12618527 · PMCID: PMC151895 · DOI:10.1172/JCI16492

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.

MeSH Terms (15)

Animals Dendritic Cells Dinoprostone Female Immunologic Deficiency Syndromes Mice Mice, Inbred BALB C Mice, Inbred C57BL Neoplasms, Experimental Neovascularization, Pathologic Prostaglandin-Endoperoxide Synthases Receptors, Prostaglandin E Receptors, Prostaglandin E, EP2 Subtype T-Lymphocytes Tumor Cells, Cultured

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