Abstract
Tumor-expressed ICAM-1 interaction with LFA-1 on naive tumor-specific CD8(+) T cells not only stabilizes adhesion, but, in the absence of classical B7-mediated costimulation, is also able to provide potent alternative costimulatory signaling resulting in the production of antitumor cytotoxic T lymphocyte (CTL) responses. This study shows that overproduction of prostaglandin (PG) E-2 by metastatic murine renal carcinoma (Renca) cells inhibited direct priming of tumor-specific CTL responses in vivo by preventing the IFN gamma-dependent upregulation of ICAM-1 that is vital during the initial priming of naive CD8(+) T cells. The addition of exogenous IFN gamma during naive CD8(+) T-cell priming abrogated PGE(2)-mediated suppression, and overexpression of ICAM-1 by tumor cells restored IFNg production and proliferation among PGE(2)-treated tumor-specific CD8(+) T cells; preventing tumor growth in vivo. These findings suggest that novel anticancer immunotherapies, which increase expression of ICAM-1 on tumor cells, could help alleviate PGE(2)-mediated immunosuppression of antitumor CTL responses. (C) 2016 AACR.