STING and Nonnecroptotic MLKL-Mediated Mechanisms Improve Dendritic Cell Maturation and Killing of Cancer Cells.

ABSTRACT: Activation of the cGAS-STING pathway plays an important role in antitumor immunity through maturation of tumor-infiltrating DCs. DCs engulf extracellular DNA released by dying cancer cells, supporting activation of the cGAS-STING pathway and concomitant DC maturation. Extracellular DNA in the tumor microenvironment is primarily derived from cells undergoing uncontrolled necrosis or programmed inflammatory death, such as necroptosis, which can be induced when apoptosis pathways are inhibited. Here, we report that caspase inhibition primes activation of a RIPK1/3, MLKL, and STING signaling axis in DCs, resulting in maturation without the need for any further maturation stimuli such as LPS or TNF-α. Notably, these signaling events do not induce DC death, indicating a nonnecroptotic role of th

SUBMITTER: Jensen TS 

PROVIDER: S-EPMC12405974 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature