STING (stimulator of interferon response cGAMP interactor 1)

L-Vac demonstrates high in vivo biosafety, breaking down into manganese ions that are primarily excreted through feces. Therefore, chiral adjuvants will pave a brilliant avenue to facilitate cancer immunotherapy.

Herein, we propose orally administrated biomimetic nanorobots with prolonged intestinal retention, enhanced mucus barrier penetration, and tumor-targeting and accumulation characteristics to treat colorectal cancer. By leveraging nanorobot motility, Salmonella-inspired targeting, CO gas-enabled metabolic modulation, and Mn2+-driven cGAS-STING activation, such biomimetic nanorobots can provoke robust radio-immunological responses, which should open a new horizon in the design of nanorobots for radio-immunotherapy.

Disrupting this interface, either by the C195S mutation or by ligand stimulation with 2'3'-cGAMP or diABZI3, relieved the tetrameric constraint and amplified STING signaling, establishing this tetramer as a duck-specific autoinhibitory assembly. These findings expand the structural repertoire of STING oligomeric assemblies, fill the structural gap for duck STING, and provide a comparative structural framework for species-specific STING regulation.

Importantly, nHA-Mn demonstrates potent tumor growth suppression and induces immune memory T cell formation while maintaining excellent biosafety profiles in vivo. Hence, this study establishes a broadly applicable therapeutic platform that uniquely integrates direct tumor cytotoxicity with self-adjuvanting immune activation, highlighting the promising potential of rational metal ion engineering in advancing next-generation cancer immunotherapy.

Mechanistically, 6-thio-dG combined with anti-PD-L1 treatment induced cGAS and PD-L1 expression and promoted immune cell infiltration in the tumors. Our findings suggest that 6-thio-dG treatment activates the cGAS-STING pathway in neuroblastoma and that induction of telomere dysfunction in combination with immune checkpoint blockade boosts intratumoral immune cell infiltration and improves survival in a high-risk neuroblastoma mouse model.

To further boost the tumoricidal effects of RT-MPs, we developed innovative chemoradiotherapy-integrated tumor cell-derived microparticles (CR-MPs) by loading RT-MPs with chemotherapeutic agents, including methotrexate (MTX), monomethyl auristatin E (MMAE), or doxorubicin (DOX). In murine MPE models, CR-MPs effectively suppressed tumor progression, extended survival, and demonstrated favorable biosafety. When combined with immunotherapy, this approach achieved a cure rate of up to 70%, induced durable immunological memory, and retained efficacy against chemotherapy-resistant tumors. This study establishes CR-MPs as a novel platform with robust therapeutic efficacy against MPE, highlighting their translational potential as a precision concurrent chemoradiotherapy strategy for MPE management in clinical settings.

STING promoter methylation and expression are linked to clinicopathological characteristics, overall survival, and immune cell infiltration in RCC. We propose that further validation of STING promoter methylation represents a biomarker for predicting responses to immune checkpoint inhibitors in RCC.

Integrating armored polydopamine delivery, genetic entanglement (STALEMATE) for biocontainment, and Gut-on-a-Chip validation, we outline a roadmap for colonic terraformation. This engineering-driven approach aims to actively reconstruct homeostasis, uniquely decoupling epithelial regeneration from tumor protection to improve long-term cancer survival.

Notably, the therapeutic effects of GPEVs were entirely abolished upon STING agonism, thereby confirming the target specificity. Our study not only establishes GPEVs as a biocompatible nanotherapeutic agent for addressing skin aging but also represents a paradigm-shifting strategy for the utilization of plant-derived extracellular vesicles, bridging critical gaps in current anti-aging dermatology.

These findings uncover a unique regulatory axis where EcOTUD5 functions as a molecular switch, differentially controlling DNA and RNA virus replication through STING stabilization and non-enzymatic mechanisms. This work provides critical insights into the role of deubiquitinases in innate immune signaling and highlights the complexity of host-virus interactions in aquatic species.

Finally, we address key translational challenges-including safety considerations, scalable manufacturing, and regulatory frameworks-that must be addressed to bridge the gap between laboratory innovation and clinical application. Collectively, these advances provide a roadmap for the next generation of smart, mechanism-driven nano-immunotherapeutics capable of transforming immunologically "cold" tumors into "hot" ones.

Arsenic trioxide (ATO)-mediated radiosensitization suppresses DDR, enhances immunogenic cell death, and increases tumor-associated antigens and cytosolic dsDNA levels...The synchronized delivery of Mn2+ and accumulated cytosolic dsDNA amplifies cGAS-STING activation, promoting dendritic cell (DC) maturation, enhancing CD8+ T cell infiltration, reducing immunosuppressive Treg infiltration, and significantly inhibiting both irradiated local tumors and non-irradiated distal CRC tumors while inducing robust immune memory effects, all with no notable toxicity. This study demonstrates that effective RT sensitization, coupled with synchronized STING activation, represents a robust strategy to overcome radio-immunotherapy resistance in colorectal cancer.