STING is an innate immune sensor for immune surveillance of viral/bacterial infection and maintenance of an immune-friendly microenvironment to prevent tumorigenesis. However, if and how STING exerts innate immunity-independent function remains elusive. Here, the authors report that STING expression is increased in renal cell carcinoma (RCC) patients and governs tumor growth through non-canonical innate immune signaling involving mitochondrial ROS maintenance and calcium homeostasis. Mitochondrial voltage-dependent anion channel VDAC2 is identified as a new STING binding partner. STING depletion potentiates VDAC2/GRP75-mediated MERC (mitochondria-ER contact) formation to increase mitochondrial ROS/calcium levels, impairs mitochondria function, and suppresses mTORC1/S6K signaling leading to RCC growth retardation. STING interaction with VDAC2 occurs through STING-C88/C91 palmitoylation and inhibiting STING palmitoyl-transferases ZDHHCs by 2-BP significantly impedes RCC cell growth alone or in combination with sorafenib. Together, these studies reveal an innate immunity-independent function of STING in regulating mitochondrial function and growth in RCC, providing a rationale to target the STING/VDAC2 interaction in treating RCC.
Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, Institute of Developmental Biology and Regenerative Medicine, College of Chemistry and Chemical Engineering, Southwest University Chongqing 400715 P. R. China
Utilizing the cGAS-STING pathway to combat immune evasion is one of the most promising strategies for enhancing cancer immunotherapy. However, current techniques for activating the cGAS-STING pathway often face a dilemma, mainly due to the balance between efficacy and safety. Here, we develop a uracil base lesion-gated dumbbell DNA nanodevice (UBLE) that allows on-demand activation and termination of the cGAS-STING pathway in tumor cells, thereby enhancing cancer immunotherapy.
TRIM14 is an important member of the TRIM family and is widely expressed in a variety of tissues. Like other members of the TRIM family, TRIM14 is also involved in ubiquitination modifications. TRIM14 was initially reported as an interferon-stimulated gene (ISG).
Introduction And Methods: Aiming to evaluate safety aspects of a recently proposed approach to target Alzheimer's disease, we mimicked a complex boron neutron capture therapy field using a mixed beam consisting of high- and low-linear energy transfer (LET) radiation, Am alpha particles (α) and/or X-ray radiation respectively, in human microglial (HMC3) cells.
Results: Acute exposure to 2 Gy X-rays induced the strongest response in the formation of γH2AX foci 30 min post irradiation, while α- and mixed beam-induced damage (α:X-ray = 3:1) sustained longer. Fractionation of the same total dose (0.
Aim: A retrospective study will review episodes of anaphylaxis during bee venom immunotherapy (BVIT) in children, any modifications made to the dosing schedule, and the subsequent outcomes over a nine-year period in Western Australia.
Methods: Patient demographics, dose eliciting anaphylaxis during BVIT, modifications made to BVIT regimen following anaphylaxis (i.e.
The activation of the STING-mediated signaling pathway leads to the secretion of type I interferon (IFN) and the activation of tumor-specific T cells. STING, a pattern recognition receptor located on the endoplasmic reticulum membrane of immune cells, binds with endogenous cyclic dinucleotides. STING undergoes phosphorylation, triggering the STING-TBK1-IRF3 pathway and NF-κB pathway, resulting in the release of IFN-β and other pro-inflammatory cytokines, ultimately enhancing the activation of tumor-specific T cells.
