Antihistamines may impact response to immune checkpoint inhibitors for cancer
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Cancer cell-derived or allergic reaction-released histamine dampened antitumor immunity and conferred resistance to cancer immunotherapy, according to a retrospective study published in Cancer Cell.
Additionally, patients with cancer who have high levels of plasma histamine may benefit from H1-antihistamine treatment in combination with immunotherapy, researchers wrote.
“There is an urgent need to improve immunotherapy efficacy. We questioned whether other common medications patients took during immunotherapy would affect the efficacy of immunotherapy,” Dihua Yu, MD, PhD, professor, biologist and Hubert L. & Olive Stringer distinguished chair in basic science, and assistant professor Yi Xiao, PhD, both in the department of molecular and cellular oncology at The University of Texas MD Anderson Cancer Center, told Healio in a joint statement.
“Our systematic analyses of patients’ health records indicated that H1-antihistamines, among a few medications, were associated with improved immunotherapy efficacy. However, uptake of H1-antihistamines was not associated with better outcomes in patients who had received chemotherapy, suggesting antihistamine is unlikely targeting cancer cells directly,” they continued.
Yu, Xiao and colleagues also discovered significantly increased histamine levels in the blood of tumor-bearing mice and patients with cancer compared with that of tumor-free mice and normal healthy individuals, which motivated them to further explore whether histamine suppresses antitumor immune response and whether antihistamines could reinvigorate antitumor immunity.
Methodology
The research team sought to determine if commonly used medications might influence responses to checkpoint inhibitors. They used clinical data from patients undergoing treatment with immune checkpoint inhibitors at MD Anderson for the retrospective analysis.
Yu, Xiao and colleagues evaluated clinical outcomes of patients with melanoma who took another medicine among 40 charted common drugs while receiving anti-PD-1/PD-L1 therapy to assess the impact of those other medications on the therapeutic response to immunotherapy.
Key findings
Results showed patients with melanoma or lung cancer taking H1-antihistamines during immunotherapy exhibited significantly improved clinical outcomes. Additionally, the clinical data suggest H1-antohistamines augment T-cell-mediated antitumor immunity.
The results surprised Yu, Xiao and fellow researchers, who anticipated allergy’s impact on antitumor immunity but not as dramatically as the results showed.
“Previously, mast cells have been the most well-known major source of histamine. We were surprised to find that cancer cells we tested so far, including cells of different cancer types from mice and humans, all secreted a significantly increased amount of histamine compared with normal cells,” the researchers told Healio. “The role of histamine in cancer initiation and progression is still not understood. Another surprising finding is that allergy reaction polarized macrophages to an immunosuppressive phenotype, which strongly inhibited antitumor immunity and converted immunotherapy-sensitive tumors to completely resistant tumors.”
Implications
The next step for Yu, Xiao and colleagues is to collaborate with physician scientists on prospective clinical studies based on the retrospective analyses. They plan to test whether adjuvant H1-antihistamine treatment enhances the response to immunotherapies in patients with cancer, particularly among those with high levels of plasma histamine.
Additionally, the results of their research opened the door to a potential link between allergic response and cancer.
“Tens of millions of people have allergies every year, but the impact of allergy response on cancer initiation and development is largely unknown,” Yu and Xiao told Healio. “We hope that more studies can reveal the impact of allergy response on cancer initiation and development.”
For more information:
Dihua Yu, MD, PhD, and Yi Xiao, PhD, can be reached at Department of Molecular and Cellular Oncology, Division of Basic Sciences, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030; email Yu at dyu@mdanderson.org; email Xiao at yxiao2@mdanderson.org.
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