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Antihistamines can influence immunotherapy response by enhancing T cell activation

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New research from The University of Texas MD Anderson Cancer Center found that treatment with antihistamines, a commonly used allergy medication, was associated with improved responses to immune checkpoint inhibitors. The preclinical study demonstrated that the histamine receptor H1 (HRH1) acts in tumor-associated macrophages (TAMs) to suppress T cell activation in the tumor microenvironment. The findings were published today in Cancer Cell.
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If replicated in prospective clinical trials, the data suggest that targeting HRH1 may be useful as a treatment approach in combination with checkpoint blockade to overcome immunotherapy resistance and improve outcomes, particularly for patients with pre-existing allergies or high plasma histamine levels.

"In searching for factors that might influence responses to immunotherapy, we were surprised to discover that antihistamines, a mediator of the allergy response, were associated with significantly improved outcomes in patients," said study co-lead Yi Xiao, Ph.D., instructor of Molecular & Cellular Oncology. "Looking closer at this relationship, we discovered that histamine, through its receptor HRH1, can promote cancer cell immune evasion and resistance to immunotherapy."

Antihistamines associated with improved immunotherapy outcomes

Immune checkpoint inhibitors, a type of immunotherapy, work by blocking certain checkpoint proteins that regulate the activity of T cells, unleashing the T cells to mount an anti-tumor response and eliminate cancer cells. Checkpoint blockade provides long-lasting responses for many patients, but not all benefit equally. Therefore, there is a desire to better understand factors that contribute to immunotherapy sensitivity or resistance.

This study began with the researchers investigating if other commonly used medications might influence responses to checkpoint inhibitors. They performed a retrospective analysis of clinical data from MD Anderson patients undergoing treatment with immune checkpoint inhibitors.

In those with melanoma or lung cancer, concurrent use of antihistamines targeting HRH1 was correlated with significantly improved survival outcomes. Patients with breast or colon cancer also displayed similar trends, although the data did not reach statistical significance due to a relatively small sample size.

Using The Cancer Genome Atlas and other publicly available patient cancer…
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