Unleashing STING: a new frontier in cancer immunotherapy

The stimulator of interferon genes (STING) pathway is a central mediator of innate immunity, sensing cytosolic DNA and triggering type I interferon responses that drive antitumor T‑cell activation. Despite the clinical success of immune checkpoint inhibitors (ICIs) such as anti‑PD‑1/PD‑L1, many cancers remain refractory due to poor tumor immunogenicity, defective T‑cell priming, or an immunosuppressive tumor microenvironment (TME). STING agonists have emerged as a powerful strategy to overcome these limitations by directly activating dendritic cells, enhancing antigen cross‑presentation, and remodeling the TME from “cold” to “hot.” Recent preclinical and early‑phase clinical studies have demonstrated that STING agonism can synergize with ICIs, chemotherapy, radiotherapy, and targeted agents, offering a promising avenue for patients with ICI‑resistant tumors.This Research Topic aims to consolidate the latest advances in STING‑targeted cancer immunotherapy, with a focus on translating mechanistic insights into clinically actionable strategies. A key challenge is the development of potent and bioavailable STING agonists that can reach the tumor or lymphoid tissues without inducing systemic toxicity. Novel delivery systems (e.g., nanoparticles, antibody‑drug conjugates, and tumor‑selective prodrugs) are being designed to overcome these hurdles. Another pressing question is how to rationally combine STING agonists with existing therapies – including ICIs, anti-angiogenic agents, chemotherapy, radiotherapy, and CAR‑T cells – to achieve durable responses. We also seek to understand resistance mechanisms that limit STING agonist efficacy, such as pathway desensitization, tumor-intrinsic epigenetic silencing, or immunosuppressive feedback loops. By gathering original research, comprehensive reviews, and clinical trial reports, this collection will define the current state of the field, identify knowledge gaps, and propose future directions. Ultimately, we aim to accelerate the clinical development of STING‑based regimens and provide a framework for patient stratification based on STING pathway integrity, tumor mutational burden, or TME immune contexture.This Research Topic welcomes studies addressing the following themes (but not limited to):1) Development and preclinical validation of novel STING agonists (synthetic, natural, or bacterial-derived)；2)Advanced delivery systems (nanoparticles, hydrogels, polymers, antibody-STING conjugates)；3)Rational combinations: STING agonists + ICIs, chemotherapy, radiotherapy, targeted therapy, or cell-based immunotherapies；4)Mechanisms of primary and acquired resistance to STING agonism；5)Biomarkers of STING pathway activation and clinical response；6)Tumor-intrinsic versus host-stromal STING signaling in cancer immunity；7)STING modulation in the context of the gut microbiome and systemic immunity；8)Early-phase clinical trials and translational studies of STING-targeting agents；；9)Natural products and traditional Chinese medicine (TCM) that modulate the STING pathway to enhance anti‑tumor immunity；10) Molecular imaging probes and visualization techniques for STING expression, activation, or therapeutic response；We invite Original Research, Review, Mini-Review, Perspective, and Clinical Trial articles. All submissions should adhere to the journal’s guidelines for Frontiers in Immunology, section Cancer Immunity and Immunotherapy.Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic. Topic editors: Zebo Jiang, Samanthi Perera, Ruonan Zhang Source: https://www.frontiersin.org/research-topics/80758/unleashing-sting-a-new-frontier-in-cancer-immunotherapy