The role of cGAS-STING signaling pathway in ferroptosis DOI Creative Commons
Lina Ding, R Zhang,

Wenqi Du

et al.

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has been identified as a crucial mechanism in antiviral defense and innate immunity pathway. Ferroptosis, characterized by iron dependence lipid peroxidation, represents specialized form cell death. A burgeoning collection studies demonstrated that the cGAS-STING participates homeostatic regulation organism modulating ferroptosis-associated enzyme activity or gene expression. Consequently, elucidating specific roles STING ferroptosis vivo is vital for targeted disease intervention. This review systematically examines interactions between ferroptosis, highlighting their influence on progression contexts inflammation, injury, cancerous dynamics. Understanding these may provide novel therapeutic strategies. implicated various death mechanisms, including apoptosis, pyroptosis, necroptosis, autophagy, ferroptosis. Our focus primarily addresses role diseases, limiting discussion other modalities precluding comprehensive overview pathway's additional functions.

Language: Английский

The crosstalk between DNA-damage responses and innate immunity DOI Creative Commons

Mei He,

Hua Jiang,

Shun Li

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 140, P. 112768 - 112768

Published: July 31, 2024

DNA damage is typically caused during cell growth by replication stress or exposure to endogenous external toxins. The accumulation of damaged causes genomic instability, which the root cause many serious disorders. Multiple cellular organisms utilize sophisticated signaling pathways against damage, collectively known as response (DDR) networks. Innate immune responses are activated following abnormalities, including damage. Interestingly, recent studies have indicated that there an intimate relationship between DDR network and innate responses. Diverse kinds cytosolic sensors, such cGAS STING, recognize induce signals related responses, link defective immunity. Moreover, components operate in IFNs and/or a cascade inflammatory cytokines via direct interactions with modulators. Consistently, factors exacerbate imbalance, resulting severe diseases, autoimmune disorders tumorigenesis. Here, latest progress understanding crosstalk reviewed. Notably, dual function modulators may provide novel insights into developing targeted immunotherapies for damage-related even carcinomas.

Language: Английский

Citations

7
Convergent inducers and effectors of T cell paralysis in the tumour microenvironment DOI
Douglas Hanahan, Olivier Michielin, Mikaël J. Pittet

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Language: Английский

Citations

6
Tissue niche influences immune and metabolic profiles to Staphylococcus aureus biofilm infection DOI Creative Commons
Zachary Van Roy, P Arumugam, Blake P. Bertrand

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 17, 2024

Infection is a devastating post-surgical complication, often requiring additional procedures and prolonged antibiotic therapy. This especially relevant for craniotomy prosthetic joint infections (PJI), both of which are characterized by biofilm formation on the bone or implant surface, respectively, with S. aureus representing primary cause. The local tissue microenvironment likely has profound effects immune attributes that can influence treatment efficacy, becomes critical to consider when developing therapeutics infections. However, extent distinct niches function during development remains relatively unknown. To address this, we compare metabolomic, transcriptomic, functional leukocytes in mouse models PJI complemented patient samples from infection modalities, reveals niche-dependent differences nucleic acid, amino lipid metabolism links modulation. These signatures spatially temporally distinct, differing not only between sites but evolving over time within single model. Collectively, this demonstrates biofilms elicit unique metabolic responses heavily influenced microenvironment, will have important implications designing therapeutic approaches targeting these

Language: Английский

Citations

5
ATM in immunobiology: From lymphocyte development to cancer immunotherapy DOI Creative Commons
Ji‐Hoon Lee

Translational Oncology, Journal Year: 2025, Volume and Issue: 52, P. 102268 - 102268

Published: Jan. 2, 2025

Language: Английский

Citations

0
Recent Mechanistic Insight into the Immunogenic Properties of Radiation-Induced Micronuclei DOI
Claire Vanpouille‐Box

International Journal of Radiation Oncology*Biology*Physics, Journal Year: 2025, Volume and Issue: 121(2), P. 283 - 286

Published: Jan. 15, 2025

Language: Английский

Citations

0
A central role of stimulator of interferon genes’ adaptor protein in defensive immune response DOI
Anju Kaushal

Immunologic Research, Journal Year: 2025, Volume and Issue: 73(1)

Published: Jan. 21, 2025

Language: Английский

Citations

0
TDP43 augments astrocyte inflammatory activity through mtDNA-cGAS-STING axis in NMOSD DOI Creative Commons

Zhuhe Liu,

Yunmeng Bai, Bingtian Xu

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 22, 2025

Abnormality in transactivating response region DNA binding protein 43 (TDP43) is well-recognized as the pathological hallmark of neurodegenerative diseases. However, role TDP43 neuromyelitis optica spectrum disorder (NMOSD) remains unknown. Here, our observations demonstrate an upregulation both vitro and vivo models NMOSD, well biological samples from NMOSD patients. Single-nucleus RNA sequencing revealed that induced A1-like reactive astrocytes astrocyte mitochondrial dysfunction mice. We further found provoked translocation to mitochondria release (mtDNA) into cytoplasm. caused activation mtDNA/cyclic GMP-AMP synthase (cGAS) / stimulator interferon genes (STING) pathway A1-type inflammatory astrocytes. Crucially, knockdown markedly ameliorated NMOSD-induced cGAS/STING Conversely, overexpression exacerbated these changes. Specific silencing astrocytic injury mice, conversely, intensified injury. Meanwhile, cGAS STING inhibitors attenuated In summary, data suggest exacerbates through upregulating mtDNA/cGAS/STING signaling pathway. Therefore, targeting represents a compelling therapeutic strategy for NMOSD.

Language: Английский

Citations

0
DNA-PK inhibition sustains the antitumor innate immune response in Small Cell Lung Cancer DOI Creative Commons
Caterina De Rosa, Floriana Morgillo, Luisa Amato

et al.

iScience, Journal Year: 2025, Volume and Issue: 28(3), P. 111943 - 111943

Published: Feb. 1, 2025

Small cell lung cancer (SCLC) is a highly aggressive form of with limited treatment options. Patients often respond well to initial chemo-immunotherapy but relapse quickly, necessitating new strategies enhance immune responsiveness. Recent research explores combining DNA-damaging therapies immunotherapy activate the STING pathway and improve antitumor response. The addition DNA Damage Repair (DDR) inhibitors, such as DNA-PKcs after chemotherapy has shown promise in activating innate sensors enhancing CD8+ T NK pathways SCLC models. This approach could potentially reshape tumor microenvironment sustain an response, offering maintenance strategy for treatment.

Language: Английский

Citations

0
The end of the genetic paradigm of cancer DOI Creative Commons
Sui Huang, Ana M. Soto,

Carlos Sonnenschein

et al.

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(3), P. e3003052 - e3003052

Published: March 18, 2025

Genome sequencing of cancer and normal tissues, alongside single-cell transcriptomics, continues to produce findings that challenge the idea is a ‘genetic disease’, as posited by somatic mutation theory (SMT). In this prevailing paradigm, tumorigenesis caused cancer-driving mutations clonal expansion. However, results from tumor sequencing, motivated genetic paradigm itself, create apparent ‘paradoxes’ are not conducive pure SMT. But beyond causation, new lend credence old ideas organismal biology. To resolve inconsistencies between biological reality, we must complement deep with thinking: embrace formal historicity entities, (re)consider non-genetic plasticity cells tissues. Essay, discuss concepts cell state dynamics tissue fields emerge collective action genes in their morphogenetic context, respectively, how they help explain data context

Language: Английский

Citations

0
NOTCH1 Mutation and Survival Analysis of Tislelizumab in Advanced or Metastatic Esophageal Squamous Cell Carcinoma: A Biomarker Analysis From the Randomized, Phase III, RATIONALE-302 Trial DOI
Xi Jiao, Wenting Du, Xi Jiao

et al.

Journal of Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

PURPOSE Although multiple agents targeting PD-1 have been approved as second-line treatment for esophageal squamous cell carcinoma (ESCC), only a fraction of patients derive long-term survival. Hence, reliable predictive biomarkers are urgently needed. METHODS Comprehensive tumor genomic profiling and transcriptome sequencing were performed on samples from the RATIONALE-302 study. We also conducted single-cell RNA analysis Notch1 knockdown ESCC murine models to further explore potential molecular mechanisms underlying anti–PD-1 benefit. RESULTS identified NOTCH1 mutation biomarker longer overall survival (OS) with tislelizumab versus chemotherapy (18.4 months v 5.3 months; hazard ratio, 0.35 [95% CI, 0.17 0.71]). At transcriptional level, type I IFN (IFN-I)/toll-like receptor expression signatures positively associated OS benefit tislelizumab, whereas B-cell neutrophil predicted unfavorable OS. Exploratory analyses showed that presence correlated enrichment IFN-I reduced infiltration B cells neutrophils. In models, comparative revealed deficiency facilitated more immunologically activated microenvironment which potentiated treatment. CONCLUSION Our data provide novel insights selection using mutations may rationale combination therapy in ESCC.

Language: Английский

Citations

0