Abstract

Natural killer (NK) cells play an important role in innate immunity to infection and tumours. NK cells have potent anti-tumour activity in vitro yet tumour cells clearly evade the action of NK cells and other immune functions in vivo.

We have analysed the mechanisms by which tumour cells inhibit the activity of NK cells using in vitro culture models and by analysis of NK cells from the human tumour microenvironment. The immunosuppresive cytokine transforming growth factor (TGF)-beta is released by tumours and inhibits NK cells during chronic interactions. In some systems, TGF -B has pro-apoptotic activity. However, NK cells are inhibited but remain viable allowing their activity to be enhanced via TGF -B blockade.

NK cells are also important in the early immune response to viral infection. However, studies of the very early events during human infection are difficult to achieve. We have analysed NK cell responses in patients receiving large timed doses of oncolytic reovirus, a dsRNA virus that infects but does not cause serious disease in humans. NK cells are activated within 24-48hrs of infection. However, NK cells also appear to play a more durable role in the immune response, expressing factors that help to shape adaptive immunity.

NK cells thus control the early stages of infection via cytotoxic activity and help to shape the adaptive immune response.