TBK1-Zyxin signaling controls tumor-associated macrophage recruitment to mitigate antitumor immunity
Although the role of innate immune sensing pathways is well-studied in the pathogenesis of malignancies, whether they influence immune cell migration is not known. This study shows that innate immune signaling via cGAS-STING or RLR-MAVS regulates tumor-associated macrophage tissue residency through activation of the TBK1-Zyxin axis.
The authors show that STING signalosomes recruit and directly phosphorylate Zyxin, thus promoting its localization to focal adhesions.
TBK1-Zyxin-mediated chemo-mechanical signaling enhances macrophage adhesion in response to cGAS-STING or RLR-MAVS signaling.
STING-TBK1-Zyxin signaling activation in mouse intratumoral tumor-associated macrophages detains TAMs in the tumor and reduces antitumor immunity responses.
Myeloid-specific or global inhibition of cGAS-STING-TBK1-Zyxin signaling facilitates antitumor immunotherapy.
https://www.embopress.org/doi/full/10.1038/s44318-024-00244-9
