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  • Title: Requirement of inositol 1,4,5-trisphosphate receptors for tumor-mediated lymphocyte apoptosis.
    Author: Steinmann C, Landsverk ML, Barral JM, Boehning D.
    Journal: J Biol Chem; 2008 May 16; 283(20):13506-9. PubMed ID: 18364356.
    Abstract:
    Tumor cells strategically down-regulate Fas receptor expression to evade immune attack and up-regulate expression of Fas ligand to promote apoptosis of infiltrating T lymphocytes. Many pathways leading to apoptotic cell death require calcium release from inositol 1,4,5-trisphosphate receptors (IP3Rs). Here, we show that Fas-dependent killing of Jurkat T lymphoma cells by SW620 colon cancer cells requires calcium release from IP3R. General suppression of IP3R signaling significantly reduced SW620-mediated Jurkat cell apoptosis. Significantly, a specific inhibitor of apoptotic calcium release from IP3R strongly blocked lymphocyte apoptosis. Thus, selective pharmacological targeting of apoptotic calcium release from IP3R may enhance tumor cell immunogenicity.
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