Williams Cancer Institute


You may have heard about cetirizine and maybe even use it when you have some allergies as it is an anti-histaminic agent well known for years. It is a second-generation histamine antagonist with a higher affinity for histamine H1 receptors; but, what’s its role in immunotherapy?

Research done in The University of Texas MD Anderson Cancer Center found that treatment with antihistamines was associated with improved responses to Immune Checkpoint Inhibitors (ICI) therapy. They found that histamine receptor H1 (HRH1) are highly expressed not in cancer cells but in certain types of tumor-associated macrophages that contribute to immune suppression; HRH1 acts in tumor-associated macrophages to suppress T cell activation in the tumor microenvironment. So, blocking HRH1 on macrophages decreased the immune-suppressive activity of the macrophages leading to an increased T cell activation and inhibition of tumor growth. This study suggests that the histamine HRH1 axis could serve as a potential biomarker of T cell dysfunction and immunotherapy response as well as promising therapeutic targets for enhancing immunotherapy response; implying that patients who have high levels of histamine in plasma that respond poorly to immunotherapies may particularly benefit from antihistamine treatment.

So by the evidence, targeting HRH1 may be useful in combination with checkpoint blockade therapy to overcome immunotherapy resistance and improve the outcomes.
There’s left to be done more studies that show or prove the efficacy of combining more antihistamine drugs with more immune checkpoint inhibitors for it to be a standard treatment and to have the best results when using immunotherapy for cancer treatment.

Reference: Hongzhong Li, Yi Xiao, Qin Li, Jun Yao, Xiangliang Yuan, Yuan Zhang, Xuedong Yin, Yohei Saito, Huihui Fan, Ping Li, Wen-Ling Kuo, Angela Halpin,Don L. Gibbons,Hideo Yagita, Zhongming Zhao, Da Pang, Guosheng Ren, Cassian Yee,  J. Jack Lee, Dihua Yu, JANUARY 10, 2022, The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1, https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00602-4

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