Anti‐tumour activity and store operated calcium entry: new roles in immunology

Abstract

Ca2+ signalling plays a critical role in almost every cell type of the immune system—T cells, B cells, NK cells, macrophages and mast cells. Intracellular Ca2+ signals in immunology have importance in both the short term and long term function of these cells. Short term functions like release of cytotoxic granules with inflammatory mediators, immune synapse formations and long term functions like cell differentiation, expression and proliferation are all regulated to various degrees by intracellular Ca2+ signals. Store operated calcium entry (SOCE) is one of the critical modulators of the Ca2+ signals that control these processes. The importance of SOCE in normal immune physiology has already been demonstrated in families with mutations in STIM1, STIM2 and Orai1 who demonstrate a severe immunodeficiency that causes bacterial, viral and fungal infections (Picard et al, 2009). Alterations in the immune system due to changes in Ca2+ homeostasis has spiked interest in studying the role of SOCE in another critical function of the immune system—anticancer immunity. Relatively little is known about SOCE and its role in oncology and the evidence gathered so far seems to suggest that it is both important in tumour detection as well as tumour growth (Prevarskaya et al, 2011). Mouse models have shown that STIM1 and Orai1 expression is critical for breast cell tumour migration and metastasis (Yang et al, 2009). Other work in human prostate cancer cells has shown that normal expression of Orai1 and SOCE are critical in maintaining the rate of apoptosis and thus, resistance to prostate cancer (Flourakis et al, 2010). Given the conflicting nature of the research in the role of SOCE in cancer immunity, it is necessary to appreciate that Ca2+ regulates a variety of complex immune functions, not all of which are cancer protective. More importantly, delineating …