STING-induced regulatory B cells compromise NK function in cancer immunity.

ABSTRACT: An immunosuppressive tumour microenvironment is a major obstacle in the control of pancreatic and other solid cancers^1-3. Agonists of the stimulator of interferon genes (STING) protein trigger inflammatory innate immune responses to potentially overcome tumour immunosuppression⁴. Although these agonists hold promise as potential cancer therapies⁵, tumour resistance to STING monotherapy has emerged in clinical trials and the mechanism(s) is unclear^5-7. Here we show that the administration of five distinct STING agonists, including cGAMP, results in an expansion of human and mouse interleukin (IL)-35⁺ regulatory B cells in pancreatic cancer. Mechanistically, cGAMP drives expression of IL-35 by B cells in an IRF3-dependent but type I inte

SUBMITTER: Li S 

PROVIDER: S-EPMC9875944 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature