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

• Published in: The Journal of clinical investigation 2003-03, Vol.111 (5), p.727-735
• Main Authors: Yang, Li, Yamagata, Noboru, Yadav, Rajwardhan, Brandon, Suzanne, Courtney, Regina L., Morrow, Jason D., Shyr, Yu, Boothby, Mark, Joyce, Sebastian, Carbone, David P., Breyer, Richard M.
• Format: Article
• Language: English
• ISSN: 0021-9738
• DOI: 10.1172/JCI200316492

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.