Prostaglandin E2 (PGE2), a major COX metabolite, plays important roles in several facets of tumor biology. We characterized the contribution of the PGE2 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, PGE2 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 PGE2, 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 PGE2-induced inhibition of DC differentiation and function and the diminished antitumor cellular immune responses in vivo.
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