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An Introduction to Immunology
In this video, Mary O’Brien (Royal Marsden Hospital, Sutton, Surrey, UK), Paul Baas (Netherlands Cancer Institute, Amsterdam) and Wilfried Eberhardt (University Hospital, Essen, Germany) outline the basics of immunotherapy.
Successful immunotherapy unleashes the body’s immune response to a tumour. A traditional approach was the therapeutic vaccine, by which a tumour antigen was administered with the aim of actively provoking an immune response to this antigen. Results in general were disappointing, as tumours could adapt to evade destruction.
The new approach – which is delivering the promising new agents - is more complex and passive. The key point is that the cancer itself is suppressing the body’s T-cell response. Programmed cell death protein-1 (PD-1 receptor) on T cells normally interacts with its ligand PD-L1 on macrophages and monocytes as part of the inflammatory response. But where PD-L1 is expressed by tumour cells, it can interact with PD-1 on the T cells and inhibit the body’s immune response. The new therapies are monoclonal antibodies which block either PD-1 or PD-L1 thereby allowing the body’s T-cells to recognise and attack tumour cells.
This at least is the working model, though researchers suspect that it will be adapted as our understanding grows. Already, a string of other relevant molecules (PD-2, PD-L2, etc) are being suggested.