Do invariant NKT (iNKT) cells offer new hope for melanoma patients?

Tumour cells are able to survive and proliferate despite the body mounting an immune response against them. Recent work by the MRC Human Immunology Unit led by Professor Vincenzo Cerundolo at the Nuffield Department of Medicine at the University of Oxford has shown that melanoma - one of the most aggressive human tumours - may have evolved a means of immune evasion by exploiting a cell mechanism that controls excessive inflammation.

In a paper published online on October 3 in Nature Immunology De Santo et al. have further characterised the properties of a subset of immune cells known as invariant NKT cells (iNKT cells). The prospect of being able to harness this population of cells could be the key to overcoming the tumour immune escape mechanism.

iNKT cells interact with other immune cells called neutrophils, cells that are able to develop according to the surrounding physiological environment. Neutrophils can be either anti-inflammatory in nature, when they suppress the immune response to non-self protein such as viruses or tumours, or they can promote inflammation, thus increasing the immune reaction to foreign proteins.

Significantly, De Santo et al. showed that melanoma cells produce a protein called serum amyloid A (SAA), a protein that is secreted by the body very early during the physiological response to infection and injury, and that this promotes the differentiation of anti-inflammatory secreting neutrophils. This has the effect of dampening the immune response both to tumours and to infections. SAA, on the other hand, also enhances the interaction of these neutrophils with iNKT cells, a process that results in the anti-inflammatory responses being overcome, thus restoring the anti-tumour immune response.

The ability to use iNKT cells to overcome the immune suppression invoked by tumour cells and infectious disease is an exciting prospect for future developments in cancer immunotherapy, and in a range of chronic and acute inflammatory diseases caused either by infection or by abnormalities in the immune system.

De Santo C, Arscott R, Booth S, Karydis I, Jones M, Asher R, Salio M, Middleton M, Cerundolo V. Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A. Nature Immunology 2010 Oct 3 [Epub ahead of print]