IFN-γ–dependent interactions between ICAM-1 and LFA-1 counteract Prostaglandin E2-mediated inhibition of anti-tumor CTL responses.

Fatemah Basingab, M Ahmadi, DJ Morgan

Research output: Contribution to journalArticle (Academic Journal)peer-review

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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 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 amongst 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 immune-suppression of antitumor CTL responses.
Translated title of the contributionPrevention of both direct and indirect priming of anti-tumor CD8+ T cell responses following over-expression of Cyclooxygenase-2 by tumour cells in vivo
Original languageEnglish
Pages (from-to)400-411
Number of pages12
JournalCancer Immunology Research
Volume4
Issue number5
Publication statusPublished - 29 Feb 2016

Bibliographical note

Publisher: AACR Publications

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