Study reveals switching off protein may boost efficacy of cancer treatment
Inhibiting a previously known protein could reduce tumour burden and enhance the effectiveness of immunotherapy treatments, a study has found.
Immunotherapy is a type of cancer treatment that boosts the body's natural defences to fight cancer.
Scientists at Johns Hopkins Kimmel Cancer Center in the US used mice genetically engineered to lack Yes-associated protein, or YAP, in several T-cell populations, including regulatory T-cells, known as Tregs.
This was the first time the relationship between YAP and Tregs has been explored, according to the research published in the journal Cancer Discovery.
Tregs are important for health, because they prevent autoimmune diseases but can be a major obstacle in the mounting of immune responses to tumours and immunotherapy.
YAP can be found in a subset of those regulatory T-cells.
Scientists tested the antitumour effects of YAP inhibitors alone and in combination with immunotherapies.
The results showed YAP plays a role in the suppression of antitumour immunity by Tregs and demonstrated by turning off YAP's abilities, tumour killing with less restrained immune cells is possible.
Fan Pan, an associate professor at Johns Hopkins Medicine, said that blocking YAP or the signalling pathways under its control boosted the effects of both a tumour vaccine and a checkpoint inhibitor (anti-PD1 antibody) to produce even stronger antitumour activity.
He said the approach of therapeutically targeting YAP was effective over a broad scope of cancer types in mice.
Tregs are notorious for dampening the effectiveness of tumour-directed immunity in cancer patients, researchers said.
The finding may pave the way for a new and promising strategy to unleash the patient immune response from the stifling grip of suppressor cell control, they said.
The researchers are optimistic that further work could lead to effective YAP-targeting immunotherapies for cancer.
They said that therapies aimed at enhancing YAP activity may have potential use for the treatment of autoimmune diseases.
