Extended Data Fig. 10: Anti-tumour effect of clonidine administered via the oral route (a,b), and schematic model of the anti-tumour activity of α2-AR agonists (c).
From: Tumour immune rejection triggered by activation of α2-adrenergic receptors
a, Progression of MC38-OVA colon carcinomas in mice treated with drinking water supplemented with clonidine (CLD) (10 μg ml−1). b, Phagocytic activity of TME macrophages from mice after 7 days of treatment as in (a) (n = 8 per group). Data (mean ± s.e.m) from one representative out of three independent experiments. P values determined by ordinary two-way ANOVA (left) and t-test (Unpaired, two-tailed, right). **** p < 0.0001. c, Model of the identified mechanisms underlying the anti-tumour activity of α2-AR agonists in the context of immunotherapy. Tumour-associated macrophages and myeloid-derived suppressor cells (MDSCs) contribute to immunosuppression in the tumour microenvironment, partly in response to factors such as adenosine and prostaglandins, which trigger the cAMP/pCREB signalling pathway. Agonists of the α2-adrenergic receptor (blue) inhibit adenylate cyclase (AC), thereby blocking the immunosuppressive cAMP/pCREB signalling. Macrophages now better stimulate anti-tumour CD4 and CD8 T cells, while MDSCs die by apoptosis. The schematic in c was created using BioRender.
