Pub Date : 2025-10-16DOI: 10.1016/j.molcel.2025.09.007
Ruochan Chen, Ju Zou, Jiao Liu, Rui Kang, Daolin Tang
Damage-associated molecular patterns (DAMPs) are endogenous molecules—such as proteins, lipids, and nucleic acids—released or exposed during cellular injury or stress, which shape immune responses by engaging danger sensors on the cell surface or within the cell interior. Recent advances have elucidated molecular links between distinct cell death pathways—apoptosis, necroptosis, pyroptosis, and ferroptosis—and DAMP release, emphasizing how biochemical features (e.g., posttranslational modifications) and temporal dynamics influence immunogenic versus tolerogenic outcomes. Here, we summarize these mechanisms, including both immunostimulatory and immunosuppressive DAMPs, and review key DAMP receptors—such as TLRs, NLRs, cGAS, and advanced glycosylation end-product-specific receptor (AGER)/RAGE—along with their downstream signaling cascades. Finally, we highlight emerging strategies to modulate DAMP signaling for cancer immunotherapy and the treatment of inflammatory diseases.
{"title":"DAMPs in the immunogenicity of cell death","authors":"Ruochan Chen, Ju Zou, Jiao Liu, Rui Kang, Daolin Tang","doi":"10.1016/j.molcel.2025.09.007","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.09.007","url":null,"abstract":"Damage-associated molecular patterns (DAMPs) are endogenous molecules—such as proteins, lipids, and nucleic acids—released or exposed during cellular injury or stress, which shape immune responses by engaging danger sensors on the cell surface or within the cell interior. Recent advances have elucidated molecular links between distinct cell death pathways—apoptosis, necroptosis, pyroptosis, and ferroptosis—and DAMP release, emphasizing how biochemical features (e.g., posttranslational modifications) and temporal dynamics influence immunogenic versus tolerogenic outcomes. Here, we summarize these mechanisms, including both immunostimulatory and immunosuppressive DAMPs, and review key DAMP receptors—such as TLRs, NLRs, cGAS, and advanced glycosylation end-product-specific receptor (AGER)/RAGE—along with their downstream signaling cascades. Finally, we highlight emerging strategies to modulate DAMP signaling for cancer immunotherapy and the treatment of inflammatory diseases.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"28 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1016/j.molcel.2025.09.014
Gaia Loucas, Nicolas Locker, Roy Parker
Mammalian cells combat pathogens by diverse mechanisms. A key aspect of host defense is the pattern recognition receptors (PRRs) that recognize foreign nucleic acids and activate innate immune signaling pathways. Dysregulation of innate immunity is associated with both infectious diseases and chronic inflammatory conditions. Recent results argue that recognition of, and signaling from, foreign nucleic acids can be modulated by the concentration of PRRs and their nucleic acid ligands into RNA/DNA-protein co-condensates. Such condensates can affect the initiation of distinct cell death programs, proinflammatory signaling, host shutdown, and the innate immune response. Given these roles, hosts and pathogens have evolved to promote or antagonize PRR-nucleic acid condensation. Moreover, general ribonucleoprotein (RNP) granules such as stress granules and paraspeckles can either promote the formation of double-stranded RNA (dsRNA) and/or influence the response to foreign nucleic acids. Herein, we discuss advances in the field that address the relationship between RNA/DNA-protein co-condensates and innate immune regulation.
哺乳动物细胞通过多种机制对抗病原体。宿主防御的一个关键方面是识别外来核酸并激活先天免疫信号通路的模式识别受体（PRRs）。先天免疫失调与感染性疾病和慢性炎症有关。最近的研究结果表明，对外来核酸的识别和信号传导可以通过PRRs及其核酸配体的浓度来调节。这些凝聚物可以影响不同细胞死亡程序的启动、促炎信号、宿主关闭和先天免疫反应。鉴于这些作用，宿主和病原体已经进化到促进或对抗prr -核酸凝聚。此外，一般核糖核蛋白（RNP）颗粒，如应激颗粒和副颗粒，可以促进双链RNA （dsRNA）的形成和/或影响对外来核酸的反应。在此，我们讨论了RNA/ dna -蛋白共凝聚物与先天免疫调节之间关系的研究进展。
{"title":"Nucleic acid-protein condensates in innate immunity","authors":"Gaia Loucas, Nicolas Locker, Roy Parker","doi":"10.1016/j.molcel.2025.09.014","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.09.014","url":null,"abstract":"Mammalian cells combat pathogens by diverse mechanisms. A key aspect of host defense is the pattern recognition receptors (PRRs) that recognize foreign nucleic acids and activate innate immune signaling pathways. Dysregulation of innate immunity is associated with both infectious diseases and chronic inflammatory conditions. Recent results argue that recognition of, and signaling from, foreign nucleic acids can be modulated by the concentration of PRRs and their nucleic acid ligands into RNA/DNA-protein co-condensates. Such condensates can affect the initiation of distinct cell death programs, proinflammatory signaling, host shutdown, and the innate immune response. Given these roles, hosts and pathogens have evolved to promote or antagonize PRR-nucleic acid condensation. Moreover, general ribonucleoprotein (RNP) granules such as stress granules and paraspeckles can either promote the formation of double-stranded RNA (dsRNA) and/or influence the response to foreign nucleic acids. Herein, we discuss advances in the field that address the relationship between RNA/DNA-protein co-condensates and innate immune regulation.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"9 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1016/j.molcel.2025.09.026
Heather Bisbee
Section snippets
Main text
In the everlasting conflict between host species and invading pathogens, innate immunity provides an early line of defense. Comprising intrinsic defensive mechanisms, innate immune systems are found across the tree of life. There is a strong appreciation of the cell types contributing to innate immune responses and the pathways that enable their function. Excitingly, interest has turned to characterizing the underlying molecular mechanisms that drive cellular immune responses and to an emphasis
{"title":"Molecular mechanisms in innate immunity","authors":"Heather Bisbee","doi":"10.1016/j.molcel.2025.09.026","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.09.026","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>In the everlasting conflict between host species and invading pathogens, innate immunity provides an early line of defense. Comprising intrinsic defensive mechanisms, innate immune systems are found across the tree of life. There is a strong appreciation of the cell types contributing to innate immune responses and the pathways that enable their function. Excitingly, interest has turned to characterizing the underlying molecular mechanisms that drive cellular immune responses and to an emphasis</section></section>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"54 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1016/j.molcel.2025.09.018
Jeremy Kean Yi Yap, Kinga Duszyc, Kate Schroder
NLRP1 (NACHT, leucine-rich repeats [LRRs], and pyrin domain [PYD]-containing protein 1) is a microbe and stress sensor that, upon activation, forms a caspase-1-activating inflammasome that drives IL-1β and IL-18 maturation and pyroptotic cell death. NLRP1 exhibits allelic diversity and interspecies differences in protein architecture, activating stimuli and expression patterns. Despite this complexity, human NLRP1 is emerging as an important sensor of perturbations in epithelial homeostasis, with key functions in epithelial inflammation, integrity, and barrier function. Here, we review recent discoveries of NLRP1 activation pathways, insights that may be gained from the related proteins caspase recruitment domain 8 (CARD8) and PIDD1, and open questions that continue to challenge the field as we move toward greater understanding of this enigmatic signaling pathway.
NLRP1 （NACHT，富含亮氨酸的重复序列[LRRs]和pyrin结构域[PYD]-containing protein 1）是一种微生物和应激传感器，激活后形成caspase-1激活炎性体，驱动IL-1β和IL-18成熟和热腐细胞死亡。NLRP1在蛋白结构、激活刺激和表达模式上表现出等位基因多样性和种间差异。尽管存在这种复杂性，人类NLRP1正在成为上皮内稳态扰动的重要传感器，在上皮炎症、完整性和屏障功能中具有关键功能。在这里，我们回顾了NLRP1激活途径的最新发现，从相关蛋白caspase募集结构域8 （CARD8）和PIDD1中可能获得的见解，以及随着我们对这一神秘信号通路的进一步了解，继续挑战该领域的开放性问题。
{"title":"NLRP1 under pressure: An overview of the NLRP1 inflammasome as a sensor of cellular stress","authors":"Jeremy Kean Yi Yap, Kinga Duszyc, Kate Schroder","doi":"10.1016/j.molcel.2025.09.018","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.09.018","url":null,"abstract":"NLRP1 (NACHT, leucine-rich repeats [LRRs], and pyrin domain [PYD]-containing protein 1) is a microbe and stress sensor that, upon activation, forms a caspase-1-activating inflammasome that drives IL-1β and IL-18 maturation and pyroptotic cell death. NLRP1 exhibits allelic diversity and interspecies differences in protein architecture, activating stimuli and expression patterns. Despite this complexity, human NLRP1 is emerging as an important sensor of perturbations in epithelial homeostasis, with key functions in epithelial inflammation, integrity, and barrier function. Here, we review recent discoveries of NLRP1 activation pathways, insights that may be gained from the related proteins caspase recruitment domain 8 (CARD8) and PIDD1, and open questions that continue to challenge the field as we move toward greater understanding of this enigmatic signaling pathway.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"1 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innate immune cells not only serve as the first line of defense against pathogen invasion but also play essential roles in the immune regulatory function of various diseases. Distinct innate immune cells and their subtypes exhibit unique metabolic profiles, and their activation, differentiation, and effector functions are tightly governed by a complex regulatory network involving both intracellular metabolism and metabolites derived from the surrounding microenvironment. Cholesterol and amino acids function not only as structural constituents of membranes and proteins but also as signaling mediators that fine-tune immune cell activity. Importantly, their metabolic pathways are tightly interconnected. This review focuses on amino acid and cholesterol metabolism, offering comprehensive insights into how these metabolic processes shape innate immune cell function during homeostasis or pathological conditions. We further discuss emerging metabolic targets and therapeutic strategies aimed at modulating innate immunity in the context of immune-related diseases.
{"title":"Amino acid and cholesterol metabolism in innate immunity","authors":"Weiyun Li, Miao Jin, Hongye Li, Ruiyue Zhong, Zhaoheng Lin, Miao Shen, Hongyan Wang","doi":"10.1016/j.molcel.2025.09.019","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.09.019","url":null,"abstract":"Innate immune cells not only serve as the first line of defense against pathogen invasion but also play essential roles in the immune regulatory function of various diseases. Distinct innate immune cells and their subtypes exhibit unique metabolic profiles, and their activation, differentiation, and effector functions are tightly governed by a complex regulatory network involving both intracellular metabolism and metabolites derived from the surrounding microenvironment. Cholesterol and amino acids function not only as structural constituents of membranes and proteins but also as signaling mediators that fine-tune immune cell activity. Importantly, their metabolic pathways are tightly interconnected. This review focuses on amino acid and cholesterol metabolism, offering comprehensive insights into how these metabolic processes shape innate immune cell function during homeostasis or pathological conditions. We further discuss emerging metabolic targets and therapeutic strategies aimed at modulating innate immunity in the context of immune-related diseases.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"1 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1016/j.molcel.2025.09.010
Yan Yan, Guangchao Liu, Qiaochu Shen, Ping He, Libo Shan
The plant immune system senses infections primarily through two branches of immune receptors: cell surface-resident pattern-recognition receptors (PRRs) and intracellular NOD-like receptors (NLRs). Although distinct in perception and activation, PRR and NLR signaling are interconnected and mutually regulated. A major class of PRRs, receptor kinases (RKs), often activate intracellular kinases, including receptor-like cytoplasmic kinases (RLCKs) and mitogen-activated protein kinases (MAPKs). Some RLCKs act as decoys, activating NLRs upon pathogen effector recognition. Recent advances expand the repertoire of kinases, including RKs, tandem kinase proteins, and calcium-dependent protein kinases, by directly activating or suppressing NLRs through phosphorylation. Furthermore, PRR-regulated RKs and MAPKs play critical roles in restraining NLR activity to maintain immune homeostasis. In response to pathogen perturbations, plants mobilize backup surveillance mechanisms involving RKs and RLCKs to derepress NLR immunity. This review highlights recent advances in the dynamic interplay between PRR and NLR signaling, focusing on protein kinases.
{"title":"Orchestration of plant PRR- and NLR-mediated immunity: Protein kinases and beyond","authors":"Yan Yan, Guangchao Liu, Qiaochu Shen, Ping He, Libo Shan","doi":"10.1016/j.molcel.2025.09.010","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.09.010","url":null,"abstract":"The plant immune system senses infections primarily through two branches of immune receptors: cell surface-resident pattern-recognition receptors (PRRs) and intracellular NOD-like receptors (NLRs). Although distinct in perception and activation, PRR and NLR signaling are interconnected and mutually regulated. A major class of PRRs, receptor kinases (RKs), often activate intracellular kinases, including receptor-like cytoplasmic kinases (RLCKs) and mitogen-activated protein kinases (MAPKs). Some RLCKs act as decoys, activating NLRs upon pathogen effector recognition. Recent advances expand the repertoire of kinases, including RKs, tandem kinase proteins, and calcium-dependent protein kinases, by directly activating or suppressing NLRs through phosphorylation. Furthermore, PRR-regulated RKs and MAPKs play critical roles in restraining NLR activity to maintain immune homeostasis. In response to pathogen perturbations, plants mobilize backup surveillance mechanisms involving RKs and RLCKs to derepress NLR immunity. This review highlights recent advances in the dynamic interplay between PRR and NLR signaling, focusing on protein kinases.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"19 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1016/j.molcel.2025.09.028
Hamid Kashkar, Manolis Pasparakis
Cells can undergo death through various genetically regulated pathways, each leading to distinct tissue outcomes. Emerging evidence suggests that these pathways are molecularly interconnected, indicating that the mode of death is determined not only by apical signals but by the availability of terminal executioners/substrates. This evolving understanding challenges the traditional rigid classification of cell death and has important implications for its therapeutic targeting in diseases.
{"title":"Cell-death networks","authors":"Hamid Kashkar, Manolis Pasparakis","doi":"10.1016/j.molcel.2025.09.028","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.09.028","url":null,"abstract":"Cells can undergo death through various genetically regulated pathways, each leading to distinct tissue outcomes. Emerging evidence suggests that these pathways are molecularly interconnected, indicating that the mode of death is determined not only by apical signals but by the availability of terminal executioners/substrates. This evolving understanding challenges the traditional rigid classification of cell death and has important implications for its therapeutic targeting in diseases.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"21 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1016/j.molcel.2025.09.016
Sara Lamorte, Matthew Bianca, Zhe Qi Liu, Tracy L. McGaha
It has been a century since it was discovered that cancer cells have a distorted metabolism compared to healthy cells and tissues. It is now universally accepted that the abnormal metabolic state of cancers is essential for proliferation and survival in the harsh environment of most solid tumors. However, the impact of the altered metabolite pools generated from this rewiring is complex and has been challenging to functionally disentangle. Macrophages are innate immune cells and a major cellular constituent of the tumor microenvironment (TME). Macrophages are functionally plastic and highly sensitive to changes in metabolite exposure, with the potential to change the TME in a profound, disease-altering fashion. However, it was not until the recent advent of sensitive, high-dimensional analysis that the impact of metabolites on tumor macrophage diversity and function was fully appreciated. In this review, we discuss recent developments in our knowledge of how altered metabolites, resulting from metabolic reprogramming in the TME, influence macrophage phenotype and the implications for tumor development and progression. Furthermore, we examine emerging therapeutic strategies aimed at targeting tumor-metabolite crosstalk to improve disease outcomes.
{"title":"Metabolites in the extracellular tumor microenvironment and the shaping of macrophage function","authors":"Sara Lamorte, Matthew Bianca, Zhe Qi Liu, Tracy L. McGaha","doi":"10.1016/j.molcel.2025.09.016","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.09.016","url":null,"abstract":"It has been a century since it was discovered that cancer cells have a distorted metabolism compared to healthy cells and tissues. It is now universally accepted that the abnormal metabolic state of cancers is essential for proliferation and survival in the harsh environment of most solid tumors. However, the impact of the altered metabolite pools generated from this rewiring is complex and has been challenging to functionally disentangle. Macrophages are innate immune cells and a major cellular constituent of the tumor microenvironment (TME). Macrophages are functionally plastic and highly sensitive to changes in metabolite exposure, with the potential to change the TME in a profound, disease-altering fashion. However, it was not until the recent advent of sensitive, high-dimensional analysis that the impact of metabolites on tumor macrophage diversity and function was fully appreciated. In this review, we discuss recent developments in our knowledge of how altered metabolites, resulting from metabolic reprogramming in the TME, influence macrophage phenotype and the implications for tumor development and progression. Furthermore, we examine emerging therapeutic strategies aimed at targeting tumor-metabolite crosstalk to improve disease outcomes.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"20 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1016/j.molcel.2025.08.030
Abraham Shim, Yanyang Chen, John Maciejowski
Genomic instability is a defining feature of cancer that fuels transformation, tumor evolution, and therapeutic resistance. However, genomic instability also incurs an immunological liability by generating cytosolic DNA, a potent trigger of cGAS-STING signaling. In this review, we summarize recent advances in our understanding of the sources of immunostimulatory cytosolic DNA in genomically unstable cancer cells. We examine how newly identified regulatory mechanisms, including chromatin-mediated cGAS suppression, influence the immune-activating potential of cytosolic DNA generated by genomic instability. We also highlight how key regulators, such as the exonuclease TREX1, may be co-opted to shield genomically unstable cancer cells from immune surveillance. By synthesizing these recent advances in our understanding of cGAS-STING activation and regulation in cancer, we aim to highlight emerging therapeutic strategies that leverage cGAS signaling to bolster antitumor immunity.
{"title":"Activation and regulation of cGAS-STING signaling in cancer cells","authors":"Abraham Shim, Yanyang Chen, John Maciejowski","doi":"10.1016/j.molcel.2025.08.030","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.08.030","url":null,"abstract":"Genomic instability is a defining feature of cancer that fuels transformation, tumor evolution, and therapeutic resistance. However, genomic instability also incurs an immunological liability by generating cytosolic DNA, a potent trigger of cGAS-STING signaling. In this review, we summarize recent advances in our understanding of the sources of immunostimulatory cytosolic DNA in genomically unstable cancer cells. We examine how newly identified regulatory mechanisms, including chromatin-mediated cGAS suppression, influence the immune-activating potential of cytosolic DNA generated by genomic instability. We also highlight how key regulators, such as the exonuclease TREX1, may be co-opted to shield genomically unstable cancer cells from immune surveillance. By synthesizing these recent advances in our understanding of cGAS-STING activation and regulation in cancer, we aim to highlight emerging therapeutic strategies that leverage cGAS signaling to bolster antitumor immunity.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"10 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1016/j.molcel.2025.09.017
Shuqi Wang, Hongyan Guo
In a recent Nature paper, Kelepouras et al.1 uncover how STING licenses ZBP1-driven necroptosis through transcriptional priming and Z-nucleic acid amplification, revealing a pathogenic circuit in SAVI and highlighting the ZBP1-RIPK3-MLKL axis as a therapeutic target.
{"title":"Caspase-8 loss stings the skin: STING drives necroptosis and interferonopathy","authors":"Shuqi Wang, Hongyan Guo","doi":"10.1016/j.molcel.2025.09.017","DOIUrl":"https://doi.org/10.1016/j.molcel.2025.09.017","url":null,"abstract":"In a recent <em>Nature</em> paper, Kelepouras et al.<span><span><sup>1</sup></span></span> uncover how STING licenses ZBP1-driven necroptosis through transcriptional priming and Z-nucleic acid amplification, revealing a pathogenic circuit in SAVI and highlighting the ZBP1-RIPK3-MLKL axis as a therapeutic target.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"13 1","pages":""},"PeriodicalIF":16.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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