Adrenergic receptors regulate T cell differentiation in viral infection and cancer

Abstract CD8 +T cells are critical components of the immune reaction against viral infections and cancer have potential to eliminate infected or malignant cells. However, when antigen persists, enter an exhausted state. Chronic disease can lead increased systemic noradrenaline (NA) levels, but it is currently still unclear how NA impacts differentiation function We here set out characterize effects β adrenergic signaling on in chronic infection with LCMV-clone 13 murine models. observed that chronically mice had elevated levels expressed higher β-1 receptor, Adrb1. impaired T cell receptor ADRB1-expressing cells, reduced proliferation function. Conversely, genetic ablation ADRB1 prevented terminal ADRB1-blockade enhanced functionality combination checkpoint blockade (ICB) ICB-sensitive melanoma model. Expanding these observations ICB-resistant model pancreatic cancer, we found pharmacological receptors synergized ICB genetically reprogram towards a tissue resident memory cell-like state improved functionality, resulting decreased tumor size. In summary, our data suggest represent novel modulates context exposure targeting may synergize patients. AMG was supported by German Research Foundation (Deutsche Forschungsgemeinschaft, GL 991/1-1). SZ K00CA222741. This work grants from NIH 5 R01 CA240909 (SMK) CA216101 (SMK).