Researchers led by the Ludwig Institute’s Benoit Van den Eynde and Jingjing Zhu reported in a June paper in Nature that existing anti-hypertensive drugs known as α2-adrenergic receptor (α2AR) agonists induce potent anti-tumor immune responses, even when they are used as monotherapies, in immunocompetent mouse models of multiple cancers. Those effects were absent in immunodeficient mouse models. They were also countered by compounds that block α2AR and significantly amplified when the agonists were combined with immunotherapy. Jingjing, Benoit and colleagues showed that the anti-tumor effects of the α2AR agonists depend on helper and killer T cells as well as macrophages, which can engulf pathogens and cancerous cells and stimulate protective T cell responses. Gene expression analysis of both cell types revealed signs of their functional activation in treated mice. Other studies established that the drugs act directly on macrophages, not cancer cells. Tumors treated with α2AR agonists showed signs of an influx of T cells and a depletion of a class of immune cells, myeloid-derived suppressor cells, that frequently gather in tumors and inhibit antitumor immune responses. The effect of the drugs extended, notably, to cancer models that have long proved resistant to standard immunotherapies.
Tumour immune rejection triggered by activation of α2-adrenergic receptors
Nature, 2023 June 7