Dr. Yi Xiao, oncology instructor at MD Anderson Cancer Center, and his associates discovered a unique role for antihistamines while searching for factors that may influence responses to immunotherapy.

As related by the ASCO Post, the team found that antihistamines, common mediators of allergy response, were responsible for improved reactions to immune checkpoint inhibitors.

The Beginning

The researchers began the study by investigating common medications they thought might bring about a response to checkpoint inhibitors. For patients with lung cancer or melanoma, the use of antihistamines that targeted HRH1 concurrently resulted in a significant increase in survival. A small group of patients with colon and breast cancer achieved similar results.

About Immune Checkpoints

Immune checkpoints regulate the immune system’s response to prevent it from destroying healthy cells. They are activated when T cells bind to other proteins such as tumor cells called immune checkpoint proteins.

When these proteins bind, an “off” signal is sent to the T cells, preventing the immune system from killing cancer cells.

A form of immunotherapy called immune checkpoint inhibitors act to block the binding of immune checkpoint proteins. The researchers analyzed clinical data from patients at MDAnderson being treated with immune checkpoint inhibitors.

Resisting Immunotherapy

In the preclinical study, scientists found that histamine can increase cancer cells’ ability to avoid the immune system and also show resistance to immunotherapy.

Macrophages are part of the immune system. They guard the immune system and respond to infectious microorganisms and injury to tissues. The histamine receptor (HRH1) acts in concert with macrophages to suppress T-cell activation.

According to Dr. Yi Xiao, the data indicates that working with HRH1 and checkpoint blockade would be advantageous in overcoming resistance to immunotherapy, especially for patients who have preexisting allergies or high plasma histamine levels.

Their findings indicate that high histamine levels, whether from cancer or allergies, could cause suppression of an antitumor response.

The researchers consulted the Cancer Genome Atlas along with other data and found a correlation between high histamine and HRH1 levels and dysfunctional T-cells, poor immunotherapy response in patients, and shorter overall survival.

Looking Forward

The team is currently designing clinical trials that will evaluate antihistamines together with checkpoint inhibitors in cancer patients.