Unmasking GARP as a Biomarker in Head and Neck Tumors

Every year, almost a million individuals are diagnosed with head and neck cancer globally, a disease known for its tenacious grip and recurring nature. Despite rigorous treatments, 40-60% of patients experience the resurgence of the tumor. With funding from the KWF for fundamental research, Dr. Rieneke van de Ven and her team will shine a spotlight on GARP, a protein receptor associated with aggressive tumor profiles in head and neck cancers.

Head and Neck Tumors are malignant growths that develop in or around the throat, larynx (voice box), nose, sinuses, and mouth. Despite the strides made in treatment, the recurrence rate of head and neck tumors remains a significant challenge.

Currently, immune checkpoint inhibitors, specifically targeting the programmed-death receptor-1 (PD-1) to invigorate the immune system to kill tumor cells, prove effective only in a minor fraction of head and neck cancer patients, ranging from 10-20%. A significant stumbling block in enhancing the success rate of treatments is the absence of a reliable biomarker that can predict the outcome of standard treatments or gauge the responsiveness towards anti-PD-1 immunotherapies.

Is GARP a biomarker?

In the quest to find a solution, a research team led by Dr. Rieneke van de Ven is shining a spotlight on the receptor GARP (glycoprotein-A repeat predominant). GARP is instrumental in facilitating the activation of Transforming growth factor-beta (TGF-β), a molecule that is known to restrain the immune system while encouraging tumor growth.

Recent investigations by the team have indicated an association between the presence of GARP in tumor cells and reduced survival rates, pointing towards an aggressive tumor profile. This research initiative aims to delve deeper, probing whether GARP's presence at the invasive front of the tumor (marginal-GARP) is indicative of a suppressed immune system, hence serving as a marker for adverse prognosis and possibly a predictor for the efficacy of anti-PD-1 therapies.

“A biomarker that can identify patients with potentially poor outcomes or those who could benefit from immunotherapy would be a significant stride forward,” says Rieneke.

Hunting for better combination therapies

The team will also investigate if restraining GARP could amplify the effectiveness of anti-PD-1 agents in combating head and neck tumors.

“Understanding GARP’s modus operandi may provide clues for new combination therapies for head and neck tumors,” says Rieneke. “In addition, we expect that site-specific information about the cells or identification of proteins or signaling pathways of interest in GARP marginal tumor cells will provide leads for novel combination treatments.”

By pinpointing the precise cellular dynamics and identifying relevant proteins or signaling pathways in GARP-positive tumor cells, the study aims to usher in a new era of combination therapies, potentially transforming the treatment paradigm for head and neck cancers.

For more information, please contact Dr. Rieneke van de Ven.

Funding by the Dutch Cancer Society.

Text by Laura Roy.

This article was created for Cancer Center Amsterdam.

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