title: IFNγ-Dependent Interactions between ICAM-1 and LFA-1 Counteract Prostaglandin E2-Mediated Inhibition of Antitumor CTL Responses.
abstract: Tumor-expressed ICAM-1 interaction with LFA-1 on naïve 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) E2 by metastatic murine renal carcinoma (Renca) cells inhibited direct priming of tumor-specific CTL responses in vivo by preventing the IFNγ-dependent upregulation of ICAM-1 that is vital during the initial priming of naïve CD8(+) T cells. The addition of exogenous IFNγ during naïve CD8(+) T-cell priming abrogated PGE2-mediated suppression, and overexpression of ICAM-1 by tumor cells restored IFNγ production and proliferation among PGE2-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 PGE2-mediated immunosuppression of antitumor CTL responses. Cancer Immunol Res; 4(5); 400-11. ©2016 AACR.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Bristol, School of Medical Sciences, Bristol, United Kingdom.
authors.forename: Fatemah Salem
authors.initials: FS
authors.lastname: Basingab
authors.affiliation: Department of Cellular and Molecular Medicine, University of Bristol, School of Medical Sciences, Bristol, United Kingdom.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ahmadi
authors.affiliation: Department of Cellular and Molecular Medicine, University of Bristol, School of Medical Sciences, Bristol, United Kingdom. d.j.morgan@bristol.ac.uk.
authors.forename: David John
authors.initials: DJ
authors.lastname: Morgan
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D015232:Dinoprostone