Targeting histamine H4 receptor improves anti-tumoral response in a murine model of breast cancer

Background: Breast cancer is one of the most common malignant tumors in women worldwide. Histamine (HIS) has been associated with either pro-tumor or anti-tumor effects, depending on the receptor evaluated. It exerts its physiological and pharmacological functions through four receptors (H1R-H4R). In breast cancer, it promotes tumor growth by activating H1 and H2 receptors. Furthermore, HIS released into the tumor microenvironment can promote inflammation associated with tumor development and immunosuppression of the immune response. Several years ago, breast cancer was shown to express the H4R, although conflicting data exist; its activation is associated with tumor progression and the development of metastases. Methods and Results: cells, the increased lymphocyte proliferation from JNJ-treated tumors, and the absence of activity in the adaptive immune-deficient Rag1 mice. Moreover, tumor-derived cells showed altered energy metabolism. Conclusion: Taken together, our results demonstrate the dual role of HIS via the H4R in 4T1 cells, modulating not only tumor cell development but also the immune microenvironment.