DNA sensing in cancer: Pro-tumour and anti-tumour functions of cGAS–STING signalling

STING agonism turns human T cells into interferon‐producing cells but impedes their functionality

(2023) Niklas Kuhl et al.   EMBO REPORTS

p53 engages the cGAS/STING cytosolic DNA sensing pathway for tumor suppression

(2023) Monisankar Ghosh et al.   MOLECULAR CELL

STING controls T cell memory fitness during infection through T cell-intrinsic and IDO-dependent mechanisms

(2023) Michael J. Quaney et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

STING agonism overcomes STAT3-mediated immunosuppression and adaptive resistance to PARP inhibition in ovarian cancer

(2023) Liya Ding et al.   Journal for ImmunoTherapy of Cancer

4-octyl itaconate as a metabolite derivative inhibits inflammation via alkylation of STING

(2023) Weizhen Li et al.   Cell Reports

STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer

(2022) Qiwei Wang et al.   Nature Communications

DDX41 is required for cGAS-STING activation against DNA virus infection

(2022) Ravi Shankar Singh et al.   Cell Reports

Epigenetic Repression of STING by MYC Promotes Immune Evasion and Resistance to Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer

(2022) Kyung-min Lee et al.   Cancer Immunology Research

Post-Translational Modifications of STING: A Potential Therapeutic Target

(2022) Jiaqi Kang et al.   Frontiers in Immunology

DNASE1L3 deficiency, new phenotypes, and evidence for a transient type I IFN signaling

(2022) Maud Tusseau et al.   JOURNAL OF CLINICAL IMMUNOLOGY

cGAS–STING drives the IL-6-dependent survival of chromosomally instable cancers

(2022) Christy Hong et al.   NATURE

A pan-cancer compendium of chromosomal instability

(2022) Ruben M. Drews et al.   NATURE

STING activation promotes robust immune response and NK cell–mediated tumor regression in glioblastoma models

(2022) Gilles Berger et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

MPS1 inhibition primes immunogenicity of KRAS-LKB1 mutant lung cancer

(2022) Shunsuke Kitajima et al.   CANCER CELL

ABCC1 transporter exports the immunostimulatory cyclic dinucleotide cGAMP

(2022) Joanna H. Maltbaek et al.   IMMUNITY

AVA-NP-695 Selectively Inhibits ENPP1 to Activate STING Pathway and Abrogate Tumor Metastasis in 4T1 Breast Cancer Syngeneic Mouse Model

(2022) Avijit Goswami et al.   MOLECULES

STING-induced regulatory B cells compromise NK function in cancer immunity

(2022) Sirui Li et al.   NATURE

DNA damage repair kinase DNA‐PK and cGAS synergize to induce cancer‐related inflammation in glioblastoma

(2022) Clara Taffoni et al.   EMBO JOURNAL

Cellular functions of cGAS-STING signaling

(2022) Chen Chen et al.   TRENDS IN CELL BIOLOGY

cGAS in nucleus: The link between immune response and DNA damage repair

(2022) Jia-Xian Song et al.   Frontiers in Immunology

5‐Fluorouracil efficacy requires anti‐tumor immunity triggered by cancer‐cell‐intrinsic STING

(2021) Jingru Tian et al.   EMBO JOURNAL

STING agonist-based treatment promotes vascular normalization and tertiary lymphoid structure formation in the therapeutic melanoma microenvironment

(2021) Manoj Chelvanambi et al.   Journal for ImmunoTherapy of Cancer

The inhibitory receptor TIM-3 limits activation of the cGAS-STING pathway in intra-tumoral dendritic cells by suppressing extracellular DNA uptake

(2021) Álvaro de Mingo Pulido et al.   IMMUNITY

TBK1 recruitment to STING activates both IRF3 and NF-κB that mediate immune defense against tumors and viral infections

(2021) Seoyun Yum et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

cGAS–STING cytosolic DNA sensing pathway is suppressed by JAK2-STAT3 in tumor cells

(2021) Manuel Adrian Suter et al.   Scientific Reports

The AIM2 and NLRP3 inflammasomes trigger IL-1–mediated antitumor effects during radiation

(2021) Chuanhui Han et al.   Science Immunology

Causes and consequences of micronuclei

(2021) Ksenia Krupina et al.   CURRENT OPINION IN CELL BIOLOGY

Human SLC46A2 Is the Dominant cGAMP Importer in Extracellular cGAMP-Sensing Macrophages and Monocytes

(2021) Anthony F. Cordova et al.   ACS Central Science

Paclitaxel Induces Micronucleation and Activates Pro-Inflammatory cGAS–STING Signaling in Triple-Negative Breast Cancer

(2021) Yang Hu et al.   MOLECULAR CANCER THERAPEUTICS

PD-L1 sustains chronic, cancer cell–intrinsic responses to type I interferon, enhancing resistance to DNA damage

(2021) HyeonJoo Cheon et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Chromatin bridges, not micronuclei, activate cGAS after drug-induced mitotic errors in human cells

(2021) Patrick J. Flynn et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

ZBP1-MLKL necroptotic signaling potentiates radiation-induced antitumor immunity via intratumoral STING pathway activation

(2021) Yuanqin Yang et al.   Science Advances

Epitope spreading driven by the joint action of CART cells and pharmacological STING stimulation counteracts tumor escape via antigen-loss variants

(2021) Enrique Conde et al.   Journal for ImmunoTherapy of Cancer

Blockade of the Phagocytic Receptor MerTK on Tumor-Associated Macrophages Enhances P2X7R-Dependent STING Activation by Tumor-Derived cGAMP

(2020) Yi Zhou et al.   IMMUNITY

Oxidized mitochondrial DNA sensing by STING signaling promotes the antitumor effect of an irradiated immunogenic cancer cell vaccine

(2020) Chunju Fang et al.   Cellular & Molecular Immunology

Molecular mechanisms and cellular functions of cGAS–STING signalling

(2020) Karl-Peter Hopfner et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Telomere Stress Potentiates STING-Dependent Anti-tumor Immunity

(2020) Ilgen Mender et al.   CANCER CELL

Interferon-Independent Activities of Mammalian STING Mediate Antiviral Response and Tumor Immune Evasion

(2020) Jianjun Wu et al.   IMMUNITY

Mitochondrial DNA drives abscopal responses to radiation that are inhibited by autophagy

(2020) Takahiro Yamazaki et al.   NATURE IMMUNOLOGY

Activation of STING by cGAMP Regulates MDSCs to Suppress Tumor Metastasis via Reversing Epithelial-Mesenchymal Transition

(2020) Hao Cheng et al.   Frontiers in Oncology

The Molecular Basis of Tight Nuclear Tethering and Inactivation of cGAS

(2020) Baoyu Zhao et al.   NATURE

Structural basis for sequestration and autoinhibition of cGAS by chromatin

(2020) Sebastian Michalski et al.   NATURE

Structural mechanism of cGAS inhibition by the nucleosome

(2020) Ganesh R. Pathare et al.   NATURE

Structural basis for the inhibition of cGAS by nucleosomes

(2020) Tomoya Kujirai et al.   SCIENCE

Structural basis of nucleosome-dependent cGAS inhibition

(2020) Joshua A. Boyer et al.   SCIENCE

Tumor-Derived cGAMP Regulates Activation of the Vasculature

(2020) Marco Campisi et al.   Frontiers in Immunology

cGAS suppresses genomic instability as a decelerator of replication forks

(2020) Hao Chen et al.   Science Advances

Overcoming resistance to STING agonist therapy to incite durable protective antitumor immunity

(2020) Henrique Lemos et al.   Journal for ImmunoTherapy of Cancer

Metastasis and immune evasion from extracellular cGAMP hydrolysis

(2020) Jun Li et al.   Cancer Discovery

The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker

(2020) Denis L. Jardim et al.   CANCER CELL

Targeting DNA Damage Response Promotes Antitumor Immunity through STING-Mediated T-cell Activation in Small Cell Lung Cancer

(2019) Triparna Sen et al.   Cancer Discovery

Autophagy induction via STING trafficking is a primordial function of the cGAS pathway

(2019) Xiang Gui et al.   NATURE

STING-mediated disruption of calcium homeostasis chronically activates ER stress and primes T cell death

(2019) Jianjun Wu et al.   JOURNAL OF EXPERIMENTAL MEDICINE

STING signaling remodels the tumor microenvironment by antagonizing myeloid-derived suppressor cell expansion

(2019) Chuan-xia Zhang et al.   CELL DEATH AND DIFFERENTIATION

SLC19A1 Is an Importer of the Immunotransmitter cGAMP

(2019) Christopher Ritchie et al.   MOLECULAR CELL

Human cGAS catalytic domain has an additional DNA-binding interface that enhances enzymatic activity and liquid-phase condensation

(2019) Wei Xie et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Chromatin‐bound cGAS is an inhibitor of DNA repair and hence accelerates genome destabilization and cell death

(2019) Hui Jiang et al.   EMBO JOURNAL

STING activation reprograms tumor vasculatures and synergizes with VEGFR2 blockade

(2019) Hannah Yang et al.   JOURNAL OF CLINICAL INVESTIGATION

SLC19A1 transports immunoreactive cyclic dinucleotides

(2019) Rutger D. Luteijn et al.   NATURE

Cancer-Cell-Intrinsic cGAS Expression Mediates Tumor Immunogenicity

(2019) Linda Schadt et al.   Cell Reports

Regulation of cGAS- and RLR-mediated immunity to nucleic acids

(2019) Andrea Ablasser et al.   NATURE IMMUNOLOGY

Structure of the Human cGAS–DNA Complex Reveals Enhanced Control of Immune Surveillance

(2018) Wen Zhou et al.   CELL

Chromosomal instability drives metastasis through a cytosolic DNA response

(2018) Samuel F. Bakhoum et al.   NATURE

Suppression of STING signaling through epigenetic silencing and missense mutation impedes DNA damage mediated cytokine production

(2018) Hiroyasu Konno et al.   ONCOGENE

DNA-induced liquid phase condensation of cGAS activates innate immune signaling

(2018) Mingjian Du et al.   SCIENCE

Exosomes Shuttle TREX1-Sensitive IFN-Stimulatory dsDNA from Irradiated Cancer Cells to DCs

(2018) Julie M. Diamond et al.   Cancer Immunology Research

The Multifaceted Role of Chromosomal Instability in Cancer and Its Microenvironment

(2018) Samuel F. Bakhoum et al.   CELL

Non-canonical NF-κB Antagonizes STING Sensor-Mediated DNA Sensing in Radiotherapy

(2018) Yuzhu Hou et al.   IMMUNITY

Non-canonical Activation of the DNA Sensing Adaptor STING by ATM and IFI16 Mediates NF-κB Signaling after Nuclear DNA Damage

(2018) Gillian Dunphy et al.   MOLECULAR CELL

Cancer Neoantigens

(2018) Ton N. Schumacher et al.   Annual Review of Immunology

PARPi Triggers the STING-Dependent Immune Response and Enhances the Therapeutic Efficacy of Immune Checkpoint Blockade Independent of BRCAness

(2018) Jianfeng Shen et al.   CANCER RESEARCH

Tumor-Derived cGAMP Triggers a STING-Mediated Interferon Response in Non-tumor Cells to Activate the NK Cell Response

(2018) Assaf Marcus et al.   IMMUNITY

Nuclear cGAS suppresses DNA repair and promotes tumorigenesis

(2018) Haipeng Liu et al.   NATURE

Magnitude of Therapeutic STING Activation Determines CD8+ T Cell-Mediated Anti-tumor Immunity

(2018) Kelsey E. Sivick et al.   Cell Reports

An Analysis of the Expression and Association with Immune Cell Infiltration of the cGAS/STING Pathway in Pan-Cancer

(2018) Xiang An et al.   Molecular Therapy-Nucleic Acids

A prosurvival DNA damage-induced cytoplasmic interferon response is mediated by end resection factors and is limited by Trex1

(2017) Erkin Erdal et al.   GENES & DEVELOPMENT

Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA for Cross-priming through Signal Regulatory Protein α Signaling

(2017) Meng Michelle Xu et al.   IMMUNITY

Intrinsic antiproliferative activity of the innate sensor STING in T lymphocytes

(2017) Silvia Cerboni et al.   JOURNAL OF EXPERIMENTAL MEDICINE

DNA-Containing Exosomes Derived from Cancer Cells Treated with Topotecan Activate a STING-Dependent Pathway and Reinforce Antitumor Immunity

(2017) Yuichi Kitai et al.   JOURNAL OF IMMUNOLOGY

Cutting Edge: Activation of STING in T Cells Induces Type I IFN Responses and Cell Death

(2017) Bridget Larkin et al.   JOURNAL OF IMMUNOLOGY

cGAS surveillance of micronuclei links genome instability to innate immunity

(2017) Karen J. Mackenzie et al.   NATURE

Mitotic progression following DNA damage enables pattern recognition within micronuclei

(2017) Shane M. Harding et al.   NATURE

Cytoplasmic chromatin triggers inflammation in senescence and cancer

(2017) Zhixun Dou et al.   NATURE

cGAS senses long and HMGB/TFAM-bound U-turn DNA by forming protein–DNA ladders

(2017) Liudmila Andreeva et al.   NATURE

Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence

(2017) Selene Glück et al.   NATURE CELL BIOLOGY

The immune contexture in cancer prognosis and treatment

(2017) Wolf H. Fridman et al.   Nature Reviews Clinical Oncology

cGAS is essential for the antitumor effect of immune checkpoint blockade

(2017) Hua Wang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Host STING-dependent MDSC mobilization drives extrinsic radiation resistance

(2017) Hua Liang et al.   Nature Communications

IFI16 is required for DNA sensing in human macrophages by promoting production and function of cGAMP

(2017) K. L. Jønsson et al.   Nature Communications

Signalling strength determines proapoptotic functions of STING

(2017) Muhammet F. Gulen et al.   Nature Communications

IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes

(2017) Jessica F. Almine et al.   Nature Communications

DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity

(2017) Claire Vanpouille-Box et al.   Nature Communications

PDL1 Signals through Conserved Sequence Motifs to Overcome Interferon-Mediated Cytotoxicity

(2017) Maria Gato-Cañas et al.   Cell Reports

Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression

(2017) Angel Garcia-Diaz et al.   Cell Reports

Recurrent Loss of STING Signaling in Melanoma Correlates with Susceptibility to Viral Oncolysis

(2016) Tianli Xia et al.   CANCER RESEARCH

Agonist-Mediated Activation of STING Induces Apoptosis in Malignant B Cells

(2016) Chih-Hang Anthony Tang et al.   CANCER RESEARCH

STING Promotes the Growth of Tumors Characterized by Low Antigenicity via IDO Activation

(2016) Henrique Lemos et al.   CANCER RESEARCH

The DNA Structure-Specific Endonuclease MUS81 Mediates DNA Sensor STING-Dependent Host Rejection of Prostate Cancer Cells

(2016) Samantha S.W. Ho et al.   IMMUNITY

Carcinoma–astrocyte gap junctions promote brain metastasis by cGAMP transfer

(2016) Qing Chen et al.   NATURE

Activation of STING requires palmitoylation at the Golgi

(2016) Kojiro Mukai et al.   Nature Communications

Deregulation of STING Signaling in Colorectal Carcinoma Constrains DNA Damage Responses and Correlates With Tumorigenesis

(2016) Tianli Xia et al.   Cell Reports

Radiotherapy Combined with Novel STING-Targeting Oligonucleotides Results in Regression of Established Tumors

(2015) J. R. Baird et al.   CANCER RESEARCH

STING Activation by Translocation from the ER Is Associated with Infection and Autoinflammatory Disease

(2015) Nicole Dobbs et al.   Cell Host & Microbe

STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity

(2015) Olivier Demaria et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation

(2015) S. Liu et al.   SCIENCE

Genome-Derived Cytosolic DNA Mediates Type I Interferon-Dependent Rejection of B Cell Lymphoma Cells

(2015) Yu J. Shen et al.   Cell Reports

Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity

(2015) Leticia Corrales et al.   Cell Reports

STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors

(2014) Seng-Ryong Woo et al.   IMMUNITY

STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors

(2014) Liufu Deng et al.   IMMUNITY

STING-Mediated DNA Sensing Promotes Antitumor and Autoimmune Responses to Dying Cells

(2014) Jared Klarquist et al.   JOURNAL OF IMMUNOLOGY

Cytosolic-DNA-Mediated, STING-Dependent Proinflammatory Gene Induction Necessitates Canonical NF- B Activation through TBK1

(2014) T. Abe et al.   JOURNAL OF VIROLOGY

Hydrolysis of 2′3′-cGAMP by ENPP1 and design of nonhydrolyzable analogs

(2014) Lingyin Li et al.   Nature Chemical Biology

DMXAA Causes Tumor Site-Specific Vascular Disruption in Murine Non-Small Cell Lung Cancer, and like the Endogenous Non-Canonical Cyclic Dinucleotide STING Agonist, 2′3′-cGAMP, Induces M2 Macrophage Repolarization

(2014) Charlene M. Downey et al.   PLoS One

IL-6 and related cytokines as the critical lynchpins between inflammation and cancer

(2014) Koji Taniguchi et al.   SEMINARS IN IMMUNOLOGY

Inflammation-driven carcinogenesis is mediated through STING

(2014) Jeonghyun Ahn et al.   Nature Communications

The Cytosolic DNA Sensor cGAS Forms an Oligomeric Complex with DNA and Undergoes Switch-like Conformational Changes in the Activation Loop

(2014) Xu Zhang et al.   Cell Reports

Structure-Function Analysis of STING Activation by c[G(2′,5′)pA(3′,5′)p] and Targeting by Antiviral DMXAA

(2013) Pu Gao et al.   CELL

IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage

(2013) HyeonJoo Cheon et al.   EMBO JOURNAL

Cyclic GMP-AMP Synthase Is Activated by Double-Stranded DNA-Induced Oligomerization

(2013) Xin Li et al.   IMMUNITY

Mouse, but not Human STING, Binds and Signals in Response to the Vascular Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid

(2013) J. Conlon et al.   JOURNAL OF IMMUNOLOGY

Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING

(2013) Xu Zhang et al.   MOLECULAR CELL

cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING

(2013) Andrea Ablasser et al.   NATURE

Structural mechanism of cytosolic DNA sensing by cGAS

(2013) Filiz Civril et al.   NATURE

Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP

(2013) Andrea Ablasser et al.   NATURE

DNA damage induces the IL-6/STAT3 signaling pathway, which has anti-senescence and growth-promoting functions in human tumors

(2012) Un Jung Yun et al.   CANCER LETTERS

Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING

(2012) Christian K Holm et al.   NATURE IMMUNOLOGY

Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation

(2012) X. Ma et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA

(2012) J. Wu et al.   SCIENCE

Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway

(2012) L. Sun et al.   SCIENCE

DNA-PK is a DNA sensor for IRF-3-dependent innate immunity

(2012) Brian J Ferguson et al.   eLife

Metastatic Cells Can Escape the Proapoptotic Effects of TNF-  through Increased Autocrine IL-6/STAT3 Signaling

(2011) S. Li et al.   CANCER RESEARCH

The Efficacy of Radiotherapy Relies upon Induction of Type I Interferon-Dependent Innate and Adaptive Immunity

(2011) B. C. Burnette et al.   CANCER RESEARCH

Host type I IFN signals are required for antitumor CD8+T cell responses through CD8α+dendritic cells

(2011) Mercedes B. Fuertes et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Type I interferon is selectively required by dendritic cells for immune rejection of tumors

(2011) Mark S. Diamond et al.   JOURNAL OF EXPERIMENTAL MEDICINE

STING is a direct innate immune sensor of cyclic di-GMP

(2011) Dara L. Burdette et al.   NATURE

The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells

(2011) Zhiqiang Zhang et al.   NATURE IMMUNOLOGY

AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC

(2009) Veit Hornung et al.   NATURE

STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity

(2009) Hiroki Ishikawa et al.   NATURE

ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization

(2009) W. Sun et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling

(2008) Hiroki Ishikawa et al.   NATURE

An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer

(2008) R. R. Weichselbaum et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA