A discovery that adds a new drug target to cancer immunotherapy has been identified by researchers from La Jolla Institute for Allergy and Immunology and their collaborators from other institutes.
The study reveals a new way to block the function of immune inhibitory checkpoint receptor CTLA-4, which is already generating a large amount of interest in the pharmaceutical and research communities due to its cancer-fighting potential.
Led by Dr Amnon Altman and Dr Kok-Fai Kong, the team demonstrated a previously unknown interaction between CTLA-4 and an intracellular enzyme protein kinase known as C-eta.
This interaction is critical for the functioning of regulatory T cells, which suppress the immune system.
While this activity is normally a useful part of a healthy immune system, preventing the body from potentially damaging immune responses that lead to autoimmune diseases, it can inhibit beneficial immune attacks against cancer.
CTLA-4 is a protein that is found on the surface of regulatory T-cells, where it plays an important role in immune suppression.
"The way it works is that this enzyme physically binds to the CTLA-4 receptor," said Dr Altman. "This binding is critical for certain suppressive functions of the regulatory T cells to proceed."
Dr Altman and his team found the enzyme must bind to CTLA-4 in order for the regulatory T cells to turn down the immune system in mice.
They also discovered that eliminating this enzyme prevented regulatory T cells from suppressing the immune system's response against a growing tumour.
Although regulatory T cells lacking protein kinase C-eta failed to inhibit an immune response against a growing tumour, they were able to continue to inhibit autoimmune disease in a mouse model of inflammatory bowel disease.
"This means that you could potentially create a therapy that would allow for a more effective immune response against cancer without the risk of increasing susceptibility to autoimmune diseases," said Dr Altman.
He added that this is important as it points to an immune mechanism specific to tumours which does not result in a response that could lead to autoimmune diseases.
Dr Altman said this is possibly due to the fact that regulatory T cells use diverse means to suppress different immune responses that do not depend on the link between C-eta and CTLA-4.