STING suppresses bone cancer pain via immune and neuronal modulation.

Journal Article (Journal Article)

Patients with advanced stage cancers frequently suffer from severe pain as a result of bone metastasis and bone destruction, for which there is no efficacious treatment. Here, using multiple mouse models of bone cancer, we report that agonists of the immune regulator STING (stimulator of interferon genes) confer remarkable protection against cancer pain, bone destruction, and local tumor burden. Repeated systemic administration of STING agonists robustly attenuates bone cancer-induced pain and improves locomotor function. Interestingly, STING agonists produce acute pain relief through direct neuronal modulation. Additionally, STING agonists protect against local bone destruction and reduce local tumor burden through modulation of osteoclast and immune cell function in the tumor microenvironment, providing long-term cancer pain relief. Finally, these in vivo effects are dependent on host-intrinsic STING and IFN-I signaling. Overall, STING activation provides unique advantages in controlling bone cancer pain through distinct and synergistic actions on nociceptors, immune cells, and osteoclasts.

Full Text

Duke Authors

Cited Authors

  • Wang, K; Donnelly, CR; Jiang, C; Liao, Y; Luo, X; Tao, X; Bang, S; McGinnis, A; Lee, M; Hilton, MJ; Ji, R-R

Published Date

  • July 27, 2021

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 4558 -

PubMed ID

  • 34315904

Pubmed Central ID

  • PMC8316360

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-021-24867-2

Language

  • eng

Conference Location

  • England