Faculty of Applied Science

The concept that the immune system can recognise tumour cells and either eliminate them (tumour immune surveillance) or select for immunologically resistant variants (immunoediting) is gaining general acceptance by immunologists. In terms of an adaptive immune response to cancer, however, much of the research has focused on the response of cytotoxic CD8+ T lymphocytes to tumour-specific antigens and the production of Th1 cytokines by CD4+ and CD8+ T cells. In contrast, Th2-mediated immunity has traditionally been viewed as favouring tumour growth, both by promoting angiogenesis and by inhibiting cell-mediated immunity and subsequent tumour cell killing. While there is evidence that components of type 2 inflammation, such as B cells and interleukin-10, do promote tumour growth, there are also many studies demonstrating the anti-tumour activity of CD4+ Th2 cells, particularly in collaboration with tumour-infiltrating granulocytes, such as eosinophils. In this review, we examine all the components of type 2 immunity and their effects on tumour growth. Collectively, from this analysis, we conclude that there is a great potential for the development of Th2-mediated immunotherapies that harness the cytotoxic activity of eosinophils.

We have previously shown that the GTP-binding protein, Gi2 of mouse Balb/c3T3 cells is linked to a serine kinase which phosphorylates the a-subunit of Gi itself. In this report we show that Gi, is coupled to a second protein kinase. This kinase does not phosphorylate G, but phosphorylates another protein bound non-covalently to Gi-. Phosphorylation of the Gi-linked protein induces its release from Gi. Kinase activity is slightly enhanced by G TPγS, suggesting that this kinase may be physiologically regulated by Gi. In an attempt to identify the kinase we have, examined the effect of peptide substrates and inhibitors on kinase activity. We found that the protein kinase A inhibitory peptide, PKI5-24, inhibited the kinase activity, but at concentrations above those usually required to block protein kinase A. The protein kinase A substrate peptide, kemptide, acted as a substrate of the kinase, and was an inhibitor of the phosphorylation of the G-linked protein. However, a protein kinase A, catalytic subunit antibody failed to react with any proteins linked to Gi. A protein kinase C inhibitory peptide had no effect on phosphorylation of the Gi-linked protein. Thus, the identity of this kinase has not been resolved, but it may form part of the signalling system of activated Gi in fibroblasts.