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ICAM-1 overexpression counteracts immune-suppress cell-derived PGE2 to restore CTL function

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)37-45
Number of pages9
JournalJournal of Immunological Sciences
Volume2
Issue number1
DateAccepted/In press - 5 Feb 2018
DatePublished (current) - 6 Feb 2018

Abstract

Tumour-infiltrating cytotoxic T lymphocytes (CTLs) play a key role in tumour killing. However, many cancers adopt various strategies to induce immunosuppression. Priming of naïve CD8+ T cells to become CTLs occurs via cognate interactions of the T cell receptor (TcR) and CD28 with tumour-derived peptide epitopes expressed on major histocompatibility complex (MHC) class I molecules and CD80/CD86 on T cells and antigen-presenting cells (APCs) respectively. Here we report that, in the absence of CD80/CD86 expression by renal carcinoma (Renca) cells, expression of intercellular adhesion molecule-1 (ICAM-1) by Renca cells provides a potent alternative co-stimulation to a tumour-specific CD8+ T cells causing them to produce interferon gamma (IFN-γ) which is crucial for the further up-regulation of ICAM-1 on tumour cells. We have shown that overexpression of cyclooxygenase-2 (COX-2), by Renca cells (Renca-T3), results in increased levels of prostaglandin (PG) E2 production, which can directly suppress anti-tumour CD8+ T cells resulting in loss of CTL function in vivo and cause metastases to the tumor-draining lymph nodes (TDLNs). Significantly, our data also show that overexpression of ICAM-1 on Renca-T3 cells can counteract the immune-suppressive effect of PGE2 and restore CTL responses.

    Research areas

  • Prostaglandin-E2 (PGE2), , Tumour microenvironment (TME), Cytotoxic T Lymphocyte (CTL), Intercellular adhesion molecule-1 (ICAM-1), Cyclooxygenase (COX-2),

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