Genomic instability, inflammatory signaling and response to cancer immunotherapy

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer - Tập 1877 Số 1 - Trang 188661 - 2022
Mengting Chen1, Renske Linstra1, Marcel A.T.M. van Vugt1
1Department of Medical Oncology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ, Groningen, the Netherlands

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Hanahan, 2011, Hallmarks of cancer: the next generation, Cell, 144, 646, 10.1016/j.cell.2011.02.013

Aguilera, 2013, Causes of genome instability, Annu. Rev. Genet., 47, 1, 10.1146/annurev-genet-111212-133232

Lawrence, 2015, DNA damage response and spindle assembly checkpoint function throughout the cell cycle to ensure genomic integrity, PLoS Genet., 11, 10.1371/journal.pgen.1005150

Brambati, 2015, Replication and transcription on a collision course: eukaryotic regulation mechanisms and implications for DNA stability, Front. Genet., 6, 166, 10.3389/fgene.2015.00166

Christensen, 2019, 5-fluorouracil treatment induces characteristic T>G mutations in human cancer, Nat. Commun., 10, 4571, 10.1038/s41467-019-12594-8

Levine, 2018, The impact of mitotic errors on cell proliferation and tumorigenesis, Genes Dev., 32, 620, 10.1101/gad.314351.118

Comaills, 2016, Genomic instability is induced by persistent proliferation of cells undergoing epithelial-to-mesenchymal transition, Cell Rep., 17, 2632, 10.1016/j.celrep.2016.11.022

Wang, 2018, Temporal DNA-PK activation drives genomic instability and therapy resistance in glioma stem cells, JCI insight, 3, 10.1172/jci.insight.98096

Davoli, 2017, Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy, Science, 355, 10.1126/science.aaf8399

Germano, 2017, Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth, Nature, 552, 116, 10.1038/nature24673

Din, 2018, Mutational analysis identifies therapeutic biomarkers in inflammatory bowel disease-associated colorectal cancers, Clin. Cancer Res., 24, 5133, 10.1158/1078-0432.CCR-17-3713

Mackenzie, 2017, cGAS surveillance of micronuclei links genome instability to innate immunity, Nature, 548, 461, 10.1038/nature23449

Pardoll, 2012, The blockade of immune checkpoints in cancer immunotherapy, Nat. Rev. Cancer, 12, 252, 10.1038/nrc3239

Postow, 2015, Immune checkpoint blockade in cancer therapy, journal of clinical oncology : official journal of the american society of, Clin. Oncol., 33, 1974

Goodman, 2017, Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers, Mol. Cancer Ther., 16, 2598, 10.1158/1535-7163.MCT-17-0386

Jenzer, 2019, The BRCA2 mutation status shapes the immune phenotype of prostate cancer, Cancer immunology, immunotherapy : CII, 68, 1621, 10.1007/s00262-019-02393-x

Chen, 2017, Elements of cancer immunity and the cancer-immune set point, Nature, 541, 321, 10.1038/nature21349

Talens, 2017, Therapeutic targeting and patient selection for cancers with homologous recombination defects, Expert Opin. Drug Discovery, 12, 565, 10.1080/17460441.2017.1322061

Wyman, 2004, Homologous recombination-mediated double-strand break repair, DNA repair, 3, 827, 10.1016/j.dnarep.2004.03.037

Ira, 2004, DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1, Nature, 431, 1011, 10.1038/nature02964

Davies, 2001, Role of BRCA2 in control of the RAD51 recombination and DNA repair protein, Mol. Cell, 7, 273, 10.1016/S1097-2765(01)00175-7

Li, 2008, Homologous recombination in DNA repair and DNA damage tolerance, Cell Res., 18, 99, 10.1038/cr.2008.1

Hickson, 2011, Processing of homologous recombination repair intermediates by the Sgs1-Top3-Rmi1 and Mus81-Mms4 complexes, Cell Cycle, 10, 3078, 10.4161/cc.10.18.16919

Schlacher, 2011, Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11, Cell, 145, 529, 10.1016/j.cell.2011.03.041

Schlacher, 2012, A distinct replication fork protection pathway connects fanconi anemia tumor suppressors to RAD51-BRCA1/2, Cancer cell, 22, 106, 10.1016/j.ccr.2012.05.015

Piazza, 2019, Homologous recombination and the formation of complex genomic rearrangements, Trends Cell Biol., 29, 135, 10.1016/j.tcb.2018.10.006

Bonadona, 2005, Contribution of BRCA1 and BRCA2 germ-line mutations to the incidence of breast cancer in young women: results from a prospective population-based study in France, Genes, Chrom. Cancer, 43, 404, 10.1002/gcc.20199

Davies, 2017, HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures, Nat. Med., 23, 517, 10.1038/nm.4292

Nguyen, 2020, Pan-cancer landscape of homologous recombination deficiency, Nature Commun., 11, 5584, 10.1038/s41467-020-19406-4

West, 2017, Genome instability as a consequence of defects in the resolution of recombination intermediates, Cold Spring Harb. Symp. Quant. Biol., 82, 207, 10.1101/sqb.2017.82.034256

Stok, 2021, Shaping the BRCAness mutational landscape by alternative double-strand break repair, replication stress and mitotic aberrancies, Nucleic Acids Res., 49, 4239, 10.1093/nar/gkab151

Stover, 2018, Association of Cell-Free DNA tumor fraction and somatic copy number alterations with survival in metastatic triple-negative breast cancer, J Clin Oncol., 36, 543, 10.1200/JCO.2017.76.0033

Roper, 2019, APOBEC mutagenesis and copy-number alterations are drivers of proteogenomic tumor evolution and heterogeneity in metastatic thoracic tumors, Cell Rep., 26, 2651, 10.1016/j.celrep.2019.02.028

Jiricny, 2006, The multifaceted mismatch-repair system, Nat. Rev. Mol. Cell Biol., 7, 335, 10.1038/nrm1907

Li, 2008, Mechanisms and functions of DNA mismatch repair, Cell Res., 18, 85, 10.1038/cr.2007.115

Martin, 2010, Therapeutic targeting of the DNA mismatch repair pathway, Clin. Cancer Res., 16, 5107, 10.1158/1078-0432.CCR-10-0821

Richman, 2015, Deficient mismatch repair: Read all about it (Review), Int. J. Oncol., 47, 1189, 10.3892/ijo.2015.3119

Jiricny, 2013, Postreplicative mismatch repair, Cold Spring Harb. Perspect. Biol., 5, 10.1101/cshperspect.a012633

Tham, 2016, Mismatch repair and homeologous recombination, DNA repair, 38, 75, 10.1016/j.dnarep.2015.11.010

Nava Rodrigues, 2018, Immunogenomic analyses associate immunological alterations with mismatch repair defects in prostate cancer, J. Clin. Invest., 128, 4441, 10.1172/JCI121924

Tamura, 2019, Genetic and genomic basis of the mismatch repair system involved in lynch syndrome, Int. J. Clin. Oncol., 24, 999, 10.1007/s10147-019-01494-y

Marabelle, 2020, Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the Phase II KEYNOTE-158 study, J. Clin. Oncol., 38, 1, 10.1200/JCO.19.02105

Risinger, 1996, Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair, Nat. Genet., 14, 102, 10.1038/ng0996-102

Battaglin, 2018, Microsatellite instability in colorectal cancer: overview of its clinical significance and novel perspectives, Clin.Adv.Hematol. Oncol.: H&O, 16, 735

Chung, 2021, DNA polymerase and mismatch repair exert distinct microsatellite instability signatures in normal and malignant human cells, Cancer Discov., 11, 1176, 10.1158/2159-8290.CD-20-0790

Guan, 2021, MLH1 deficiency-triggered DNA hyperexcision by exonuclease 1 activates the cGAS-STING pathway, Cancer Cell, 39, 10.1016/j.ccell.2020.11.004

Germano, 2018, The clinical impact of the genomic landscape of mismatch repair-deficient cancers, Cancer Discov., 8, 1518, 10.1158/2159-8290.CD-18-0150

Gaillard, 2015, Replication stress and cancer, Nat. Rev. Cancer, 15, 276, 10.1038/nrc3916

Tsantoulis, 2008, Oncogene-induced replication stress preferentially targets common fragile sites in preneoplastic lesions.A genome-wide study, Oncogene, 27, 3256, 10.1038/sj.onc.1210989

Bester, 2011, Nucleotide deficiency promotes genomic instability in early stages of cancer development, Cell, 145, 435, 10.1016/j.cell.2011.03.044

Coquel, 2018, SAMHD1 acts at stalled replication forks to prevent interferon induction, Nature, 557, 57, 10.1038/s41586-018-0050-1

Kotsantis, 2018, Mechanisms of oncogene-induced replication stress: Jigsaw falling into place, Cancer discovery, 8, 537, 10.1158/2159-8290.CD-17-1461

Burrell, 2013, Replication stress links structural and numerical cancer chromosomal instability, Nature, 494, 492, 10.1038/nature11935

Xu, 2011, Replication stress induces micronuclei comprising of aggregated DNA double-strand breaks, PloS one, 6

Jones, 2013, Increased replication initiation and conflicts with transcription underlie cyclin E-induced replication stress, Oncogene, 32, 3744, 10.1038/onc.2012.387

Macheret, 2018, Intragenic origins due to short G1 phases underlie oncogene-induced DNA replication stress, Nature, 555, 112, 10.1038/nature25507

Di Micco, 2006, Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication, Nature, 444, 638, 10.1038/nature05327

Macheret, 2020, High-resolution mapping of mitotic DNA synthesis regions and common fragile sites in the human genome through direct sequencing, Cell Res., 30, 997, 10.1038/s41422-020-0358-x

Menghi, 2018, The tandem duplicator phenotype is a prevalent genome-wide cancer configuration driven by distinct gene mutations, Cancer cell, 34, 197, 10.1016/j.ccell.2018.06.008

Lara-Gonzalez, 2012, The spindle assembly checkpoint, Current Biol. : CB, 22, R966, 10.1016/j.cub.2012.10.006

Drost, 2015, Sequential cancer mutations in cultured human intestinal stem cells, Nature, 521, 43, 10.1038/nature14415

Bolhaqueiro, 2019, Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids, Nat. Genet., 51, 824, 10.1038/s41588-019-0399-6

Lee, 2011, Chromosomal instability confers intrinsic multidrug resistance, Cancer Res., 71, 1858, 10.1158/0008-5472.CAN-10-3604

Janssen, 2011, Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations, Science, 333, 1895, 10.1126/science.1210214

Umbreit, 2020, Mechanisms generating cancer genome complexity from a single cell division error, Science, 368, 10.1126/science.aba0712

Nassour, 2019, Autophagic cell death restricts chromosomal instability during replicative crisis, Nature, 565, 659, 10.1038/s41586-019-0885-0

Hayflick, 1965, The limited in vitro lifetime of human diploid cell strains, Exp. Cell Res., 37, 614, 10.1016/0014-4827(65)90211-9

Frias, 2012, Telomere dysfunction and genome instability, Front.B iosci. (Landmark edition), 17, 2181, 10.2741/4044

McClintock, 1938, The production of homozygous deficient tissues with mutant characteristics by means of the aberrant mitotic behavior of ring-shaped chromosomes, Genetics, 23, 315, 10.1093/genetics/23.4.315

Petros, 2005, mtDNA mutations increase tumorigenicity in prostate cancer, Proc. Natl. Acad. Sci. U. S. A., 102, 719, 10.1073/pnas.0408894102

Tadi, 2016, Microhomology-mediated end joining is the principal mediator of double-strand break repair during mitochondrial DNA lesions, Mol. Biol. Cell, 27, 223, 10.1091/mbc.e15-05-0260

Dahal, 2018, Homologous recombination-mediated repair of DNA double-strand breaks operates in mammalian mitochondria, Cell. Mol.Life Sci.: CMLS, 75, 1641, 10.1007/s00018-017-2702-y

Shokolenko, 2013, Persistent damage induces mitochondrial DNA degradation, DNA repair, 12, 488, 10.1016/j.dnarep.2013.04.023

Ichim, 2015, Limited mitochondrial permeabilization causes DNA damage and genomic instability in the absence of cell death, Mol. Cell, 57, 860, 10.1016/j.molcel.2015.01.018

Taylor, 2005, Mitochondrial DNA mutations in human disease, Nat. Rev. Genet., 6, 389, 10.1038/nrg1606

Hatch, 2013, Catastrophic nuclear envelope collapse in cancer cell micronuclei, Cell, 154, 47, 10.1016/j.cell.2013.06.007

Lewis, 2016, Cancer cells that survive checkpoint adaptation contain micronuclei that harbor damaged DNA, cell cycle (Georgetown, Tex.), 15, 3131

Crasta, 2012, DNA breaks and chromosome pulverization from errors in mitosis, Nature, 482, 53, 10.1038/nature10802

Zhang, 2015, Chromothripsis from DNA damage in micronuclei, Nature, 522, 179, 10.1038/nature14493

Tigano, 2021, Nuclear sensing of breaks in mitochondrial DNA enhances immune surveillance, Nature, 591, 477, 10.1038/s41586-021-03269-w

Chabanon, 2021, Targeting the DNA damage response in immuno-oncology: developments and opportunities, Nat. Rev. Cancer, 21, 701, 10.1038/s41568-021-00386-6

Galluzzi, 2018, SnapShot: CGAS-STING signaling, Cell, 173, 10.1016/j.cell.2018.03.015

Zhao, 2019, A conserved PLPLRT/SD motif of STING mediates the recruitment and activation of TBK1, Nature, 569, 718, 10.1038/s41586-019-1228-x

Sun, 2013, Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway, Science (New York, N.Y.), 339, 786, 10.1126/science.1232458

Balka, 2020, TBK1 and IKKε act redundantly to mediate STING-induced NF-κB responses in myeloid cells, Cell Rep., 31, 10.1016/j.celrep.2020.03.056

Harding, 2017, Mitotic progression following DNA damage enables pattern recognition within micronuclei, Nature, 548, 466, 10.1038/nature23470

Zierhut, 2019, The cytoplasmic DNA sensor cGAS promotes mitotic cell death, Cell, 178, 302, 10.1016/j.cell.2019.05.035

Li, 2021, Phosphorylation and chromatin tethering prevent cGAS activation during mitosis, Science, 371, 10.1126/science.abc5386

Feng, 2020, ATR inhibition potentiates ionizing radiation-induced interferon response via cytosolic nucleic acid-sensing pathways, EMBO J., 39, 10.15252/embj.2019104036

Liu, 2019, Cytoplasm and beyond: dynamic innate immune sensing of influenza a virus by RIG-I, J. Virol., 93, 10.1128/JVI.02299-18

Kouwaki, 2017, Zyxin stabilizes RIG-I and MAVS interactions and promotes type I interferon response, Sci. Rep., 7, 11905, 10.1038/s41598-017-12224-7

Liu, 2015, Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation, Science, 347, 10.1126/science.aaa2630

Chiu, 2009, RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway, Cell, 138, 576, 10.1016/j.cell.2009.06.015

Wang, 2015, Cytosolic dsDNA triggers apoptosis and pro-inflammatory cytokine production in normal human melanocytes, Exp. Dermatol., 24, 298, 10.1111/exd.12621

Zevini, 2017, Crosstalk between cytoplasmic RIG-I and STING sensing pathways, Trends Immunol., 38, 194, 10.1016/j.it.2016.12.004

Yadav, 2014, Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing, Nature, 515, 572, 10.1038/nature14001

Heijink, 2019, BRCA2 deficiency instigates cGAS-mediated inflammatory signaling and confers sensitivity to tumor necrosis factor-alpha-mediated cytotoxicity, Nat. Commun., 10, 100, 10.1038/s41467-018-07927-y

Reislander, 2019, BRCA2 abrogation triggers innate immune responses potentiated by treatment with PARP inhibitors, Nat. Commun., 10, 3143, 10.1038/s41467-019-11048-5

Parkes, 2017, Activation of STING-dependent innate immune signaling by S-phase-specific DNA damage in breast cancer, J. Natl. Cancer Inst., 109, 10.1093/jnci/djw199

Schadt, 2019, Cancer-cell-intrinsic cGAS expression mediates tumor immunogenicity, Cell Rep., 29, 1236, 10.1016/j.celrep.2019.09.065

de Oliveira Mann, 2019, Modular architecture of the STING C-terminal tail allows interferon and NF-kappaB signaling adaptation, Cell Rep., 27, 1165, 10.1016/j.celrep.2019.03.098

Seth, 2005, Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3, Cell, 122, 669, 10.1016/j.cell.2005.08.012

Zhao, 2016, Structural basis for concerted recruitment and activation of IRF-3 by innate immune adaptor proteins, Proc. Natl. Acad. Sci. U. S. A., 113, 10.1073/pnas.1603269113

Andrilenas, 2018, DNA-binding landscape of IRF3, IRF5 and IRF7 dimers: implications for dimer-specific gene regulation, Nucleic Acids Res., 46, 2509, 10.1093/nar/gky002

DiDonato, 2012, NF-κB and the link between inflammation and cancer, Immunol. Rev., 246, 379, 10.1111/j.1600-065X.2012.01099.x

Hou, 2018, Non-canonical NF-κB antagonizes STING sensor-mediated DNA sensing in radiotherapy, Immunity, 49, 490, 10.1016/j.immuni.2018.07.008

Laulier, 2011, The relative efficiency of homology-directed repair has distinct effects on proper anaphase chromosome separation, Nucleic Acids Res., 39, 5935, 10.1093/nar/gkr187

Schoonen, 2019, Premature mitotic entry induced by ATR inhibition potentiates olaparib inhibition-mediated genomic instability, inflammatory signaling, and cytotoxicity in BRCA2-deficient cancer cells, Mol. Oncol., 13, 2422, 10.1002/1878-0261.12573

Kaufman, 2015, Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation, J. Clin. Oncol., 33, 244, 10.1200/JCO.2014.56.2728

Bryant, 2005, Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase, Nature, 434, 913, 10.1038/nature03443

Farmer, 2005, Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy, Nature, 434, 917, 10.1038/nature03445

Chabanon, 2019, PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer, J. Clin. Invest., 129, 1211, 10.1172/JCI123319

Chen, 2020, Cell cycle checkpoints cooperate to suppress DNA- and RNA-associated molecular pattern recognition and anti-tumor immune responses, Cell Rep., 32, 10.1016/j.celrep.2020.108080

Ghosh, 2018, PARP1 depletion induces RIG-I-dependent signaling in human cancer cells, PloS one, 13, 10.1371/journal.pone.0194611

Guo, 2021, Reciprocal regulation of RIG-I and XRCC4 connects DNA repair with RIG-I immune signaling, Nat. Commun., 12, 2187, 10.1038/s41467-021-22484-7

Kondo, 2013, DNA damage sensor MRE11 recognizes cytosolic double-stranded DNA and induces type I interferon by regulating STING trafficking, Proc. Natl. Acad. Sci. U. S. A., 110, 2969, 10.1073/pnas.1222694110

Pantelidou, 2019, PARP inhibitor efficacy depends on CD8(+) T-cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer, Cancer Discov., 9, 722, 10.1158/2159-8290.CD-18-1218

Ding, 2018, PARP inhibition elicits STING-dependent antitumor immunity in Brca1-deficient ovarian cancer, Cell Rep., 25, 2972, 10.1016/j.celrep.2018.11.054

Ceccaldi, 2015, Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair, Nature, 518, 258, 10.1038/nature14184

Li, 2021, Depletion of DNA polymerase theta inhibits tumor growth and promotes genome instability through the cGAS-STING-ISG pathway in esophageal squamous cell carcinoma, Cancers, 13, 3204, 10.3390/cancers13133204

Mackenzie, 2016, Ribonuclease H2 mutations induce a cGAS/STING-dependent innate immune response, EMBO J., 35, 831, 10.15252/embj.201593339

Ishikawa, 2008, STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling, Nature, 455, 674, 10.1038/nature07317

Parkes, 2021, The clinical and molecular significance associated with STING signaling in breast cancer, NPJ Breast Cancer, 7, 81, 10.1038/s41523-021-00283-z

Mukai, 2016, Activation of STING requires palmitoylation at the golgi, Nat. Commun., 7, 11932, 10.1038/ncomms11932

Dunphy, 2018, Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-kappaB signaling after nuclear DNA damage, Mol. Cell, 71, 10.1016/j.molcel.2018.07.034

Dixon, 2021, STING nuclear partners contribute to innate immune signaling responses, iScience, 24, 10.1016/j.isci.2021.103055

Veuger, 2009, Ionizing radiation-induced NF-kappaB activation requires PARP-1 function to confer radioresistance, Oncogene, 28, 832, 10.1038/onc.2008.439

Abe, 2014, Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-kappaB activation through TBK1, J. Virol., 88, 5328, 10.1128/JVI.00037-14

Bakhoum, 2018, The multifaceted role of chromosomal instability in cancer and its microenvironment, Cell, 174, 1347, 10.1016/j.cell.2018.08.027

Jin, 2020, Chromosomal instability upregulates interferon in acute myeloid leukemia, Genes, chromosomes & cancer, 59, 627, 10.1002/gcc.22880

Krivega, 2021, Genotoxic stress in constitutive trisomies induces autophagy and the innate immune response via the cGAS-STING pathway, Commun. Biol., 4, 831, 10.1038/s42003-021-02278-9

Andriani, 2016, Whole chromosome instability induces senescence and promotes SASP, Sci. Rep., 6, 35218, 10.1038/srep35218

Dou, 2017, Cytoplasmic chromatin triggers inflammation in senescence and cancer, Nature, 550, 402, 10.1038/nature24050

Bakhoum, 2018, Chromosomal instability drives metastasis through a cytosolic DNA response, Nature, 553, 467, 10.1038/nature25432

Basit, 2020, The cGAS/STING/TBK1/IRF3 innate immunity pathway maintains chromosomal stability through regulation of p21 levels, Exp. Mol. Med., 52, 643, 10.1038/s12276-020-0416-y

Gius, 2019, Homeostatic roles of STING in cell proliferation and chromosomal instability, Cancer Res., 79, 1295, 10.1158/0008-5472.CAN-19-0212

Riley, 2020, Mitochondrial DNA in inflammation and immunity, EMBO Rep., 21, 10.15252/embr.201949799

West, 2015, Mitochondrial DNA stress primes the antiviral innate immune response, Nature, 520, 553, 10.1038/nature14156

Wu, 2019, Mitochondrial DNA stress signalling protects the nuclear genome, Nature metabolism, 1, 1209, 10.1038/s42255-019-0150-8

Rongvaux, 2014, Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA, Cell, 159, 1563, 10.1016/j.cell.2014.11.037

Yan-Fei, 2020, Dysregulation in nucleic acid-sensing pathway genes is associated with cancer patients' prognosis, Cancer Sci., 111, 2212, 10.1111/cas.14450

Ghaffari, 2018, STING agonist therapy in combination with PD-1 immune checkpoint blockade enhances response to carboplatin chemotherapy in high-grade serous ovarian cancer, Br. J. Cancer, 119, 440, 10.1038/s41416-018-0188-5

Wang, 2017, cGAS is essential for the antitumor effect of immune checkpoint blockade, Proc. Natl. Acad. Sci. U. S. A., 114, 1637, 10.1073/pnas.1621363114

Katlinskaya, 2016, Suppression of type I interferon signaling overcomes oncogene-induced senescence and mediates melanoma development and progression, Cell Rep., 15, 171, 10.1016/j.celrep.2016.03.006

Diamond, 2011, Type I interferon is selectively required by dendritic cells for immune rejection of tumors, J. Exp. Med., 208, 1989, 10.1084/jem.20101158

Marcus, 2018, Tumor-derived cGAMP triggers a STING-mediated interferon response in non-tumor cells to activate the NK cell response, Immunity, 49, 754, 10.1016/j.immuni.2018.09.016

Strickland, 2016, Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer, Oncotarget, 7, 13587, 10.18632/oncotarget.7277

Wen, 2019, Association of BRCA1- and BRCA2-deficiency with mutation burden, expression of PD-L1/PD-1, immune infiltrates, and T cell-inflamed signature in breast cancer, PloS one, 14, 10.1371/journal.pone.0215381

Samstein, 2021, Mutations in BRCA1 and BRCA2 differentially affect the tumor microenvironment and response to checkpoint blockade immunotherapy, Nature cancer, 1, 1188, 10.1038/s43018-020-00139-8

George, 2013, Nonequivalent gene expression and copy number alterations in high-grade serous ovarian cancers with BRCA1 and BRCA2 mutations, Clin. Cancer Res.: Off. J. Am. Assoc.Cancer Res., 19, 3474, 10.1158/1078-0432.CCR-13-0066

Zhou, 2021, Evaluation of BRCA1 and BRCA2 as indicators of response to immune checkpoint inhibitors, JAMA Netw. Open, 4, 10.1001/jamanetworkopen.2021.7728

Wang, 2019, cGAS/STING axis mediates a topoisomerase II inhibitor-induced tumor immunogenicity, J. Clin. Invest., 130, 4850, 10.1172/JCI127471

Touat, 2018, DNA repair deficiency sensitizes lung cancer cells to NAD+ biosynthesis blockade, J. Clin. Invest., 128, 1671, 10.1172/JCI90277

Kim, 2020, PARP1 inhibitors trigger innate immunity via PARP1 trapping-induced DNA damage response, eLife, 9, 10.7554/eLife.60637

Shen, 2019, PARPi triggers the STING-dependent immune response and enhances the therapeutic efficacy of immune checkpoint blockade independent of BRCAness, Cancer Res., 79, 311, 10.1158/0008-5472.CAN-18-1003

Manguso, 2017, In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target, Nature, 547, 413, 10.1038/nature23270

Patel, 2017, Identification of essential genes for cancer immunotherapy, Nature, 548, 537, 10.1038/nature23477

Wang, 2021, Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells, EMBO Rep., 22, 10.15252/embr.202052032

Liang, 2017, Host STING-dependent MDSC mobilization drives extrinsic radiation resistance, Nat. Commun., 8, 1736, 10.1038/s41467-017-01566-5

An, 2019, An analysis of the expression and association with immune cell infiltration of the cGAS/STING pathway in pan-cancer, Molecular therapy. Nucleic acids, 14, 80, 10.1016/j.omtn.2018.11.003

Przybytkowski, 2020, An immune-centric exploration of BRCA1 and BRCA2 germline mutation related breast and ovarian cancers, BMC Cancer, 20, 197, 10.1186/s12885-020-6605-1

Samstein, 2019, Tumor mutational load predicts survival after immunotherapy across multiple cancer types, Nat. Genet., 51, 202, 10.1038/s41588-018-0312-8

Cardenas, 2019, Interferon-γ signaling is associated with BRCA1 loss-of-function mutations in high grade serous ovarian cancer, NPJ Precision Oncol., 3, 32, 10.1038/s41698-019-0103-4

Garcia-Diaz, 2017, Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression, Cell Rep., 19, 1189, 10.1016/j.celrep.2017.04.031

Lu, 2017, JAK-STAT-mediated chronic inflammation impairs cytotoxic T lymphocyte activation to decrease anti-PD-1 immunotherapy efficacy in pancreatic cancer, Oncoimmunology, 6, 10.1080/2162402X.2017.1291106

Aguadé-Gorgorió, 2019, Genetic instability as a driver for immune surveillance, J.Immunotherapy Cancer, 7, 345, 10.1186/s40425-019-0795-6

Talens, 2019, Inflammatory signaling in genomically instable cancers, Cell cycle (Georgetown, Tex.), 18, 1830, 10.1080/15384101.2019.1638192

Gerlinger, 2010, How darwinian models inform therapeutic failure initiated by clonal heterogeneity in cancer medicine, Br. J. Cancer, 103, 1139, 10.1038/sj.bjc.6605912

Tobalina, 2021, A meta-analysis of reversion mutations in BRCA genes identifies signatures of DNA end-joining repair mechanisms driving therapy resistance, Ann. Oncol., 32, 103, 10.1016/j.annonc.2020.10.470

Adam, 2021, CIP2A is a prime synthetic-lethal target for BRCA-mutated cancers, bioRxiv

Zompit, 2021, The CIP2A-TOPBP1 complex safeguards chromosomal stability during mitosis, bioRxiv

Krajewska, 2015, ATR inhibition preferentially targets homologous recombination-deficient tumor cells, Oncogene, 34, 3474, 10.1038/onc.2014.276

Vanpouille-Box, 2017, DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity, Nat. Commun., 8, 15618, 10.1038/ncomms15618

Vanpouille-Box, 2017, TREX1 dictates the immune fate of irradiated cancer cells, Oncoimmunology, 6, 10.1080/2162402X.2017.1339857

Bartsch, 2017, Absence of RNase H2 triggers generation of immunogenic micronuclei removed by autophagy, Hum. Mol. Genet., 26, 3960, 10.1093/hmg/ddx283

Rello-Varona, 2012, Autophagic removal of micronuclei, Cell cycle, 11, 170, 10.4161/cc.11.1.18564

Konno, 2018, Suppression of STING signaling through epigenetic silencing and missense mutation impedes DNA damage mediated cytokine production, Oncogene, 37, 2037, 10.1038/s41388-017-0120-0

Ma, 2020, LncRNA NEAT1 interacted with DNMT1 to regulate malignant phenotype of cancer cell and cytotoxic T cell infiltration via epigenetic inhibition of p53, cGAS, and STING in lung cancer, Front. Genet., 11, 250, 10.3389/fgene.2020.00250

Kitajima, 2019, Suppression of STING associated with LKB1 loss in KRAS-driven lung cancer, Cancer Discovery, 9, 34, 10.1158/2159-8290.CD-18-0689

Xia, 2016, Deregulation of STING signaling in colorectal carcinoma constrains DNA damage responses and correlates with tumorigenesis, Cell Rep., 14, 282, 10.1016/j.celrep.2015.12.029

Song, 2017, Decreased expression of STING predicts poor prognosis in patients with gastric cancer, Sci. Rep., 7, 39858, 10.1038/srep39858

Hong, 2019, The cGAS paradox: contrasting roles for cGAS-STING pathway in chromosomal instability, Cells, 8, 1228, 10.3390/cells8101228

Li, 2020, Metastasis and immune evasion from extracellular cGAMP hydrolysis, Cancer Discov., 11, 1212, 10.1158/2159-8290.CD-20-0387

Annunziato, 2019, Comparative oncogenomics identifies combinations of driver genes and drug targets in BRCA1-mutated breast cancer, Nat. Commun., 10, 397, 10.1038/s41467-019-08301-2

2012, 490, 61

Casey, 2018, The MYC oncogene is a global regulator of the immune response, Blood, 131, 2007, 10.1182/blood-2017-11-742577

Sodir, 2020, MYC instructs and maintains pancreatic adenocarcinoma phenotype, Cancer Discovery, 10, 588, 10.1158/2159-8290.CD-19-0435

Muthalagu, 2020, Repression of the type I interferon pathway underlies MYC- and KRAS-dependent evasion of NK and B cells in pancreatic ductal adenocarcinoma, Cancer Discovery, 10, 872, 10.1158/2159-8290.CD-19-0620

Swaminathan, 2020, MYC functions as a switch for natural killer cell-mediated immune surveillance of lymphoid malignancies, Nat. Commun., 11, 2860, 10.1038/s41467-020-16447-7

Casey, 2016, MYC regulates the antitumor immune response through CD47 and PD-L1, Science, 352, 227, 10.1126/science.aac9935

Vaseva, 2018, KRAS suppression-induced degradation of MYC is antagonized by a MEK5-ERK5 compensatory mechanism, Cancer Cell, 34, 807, 10.1016/j.ccell.2018.10.001

Zdanov, 2016, Mutant KRAS conversion of conventional T cells into regulatory T cells, Cancer Immunol.Research, 4, 354, 10.1158/2326-6066.CIR-15-0241

Liao, 2019, KRAS-IRF2 Axis drives immune suppression and immune therapy resistance in colorectal cancer, Cancer Cell, 35, 559, 10.1016/j.ccell.2019.02.008

Ghosh, 2021, Mutant p53 suppresses innate immune signaling to promote tumorigenesis, Cancer Cell, 39, 494, 10.1016/j.ccell.2021.01.003

Reck, 2016, Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer, N. Engl. J. Med., 375, 1823, 10.1056/NEJMoa1606774

Hellmann, 2019, Nivolumab plus ipilimumab in advanced non-small-cell lung cancer, N. Engl. J. Med., 381, 2020, 10.1056/NEJMoa1910231

André, 2020, Pembrolizumab in microsatellite-instability-high advanced colorectal cancer, N. Engl. J. Med., 383, 2207, 10.1056/NEJMoa2017699

Hsiehchen, 2020, DNA repair gene mutations as predictors of immune checkpoint inhibitor response beyond tumor mutation burden, Cell Rep. Med., 1, 100034, 10.1016/j.xcrm.2020.100034

Ricciuti, 2020, Impact of DNA damage response and repair (DDR) gene mutations on efficacy of PD-(L)1 immune checkpoint inhibition in non-small cell lung cancer, Clin. Cancer Res., 26, 4135, 10.1158/1078-0432.CCR-19-3529

Galati, 2020, Cancers from novel pole-mutant mouse models provide insights into polymerase-mediated hypermutagenesis and immune checkpoint blockade, Cancer Res., 80, 5606, 10.1158/0008-5472.CAN-20-0624

Grabosch, 2019, Cisplatin-induced immune modulation in ovarian cancer mouse models with distinct inflammation profiles, Oncogene, 38, 2380, 10.1038/s41388-018-0581-9

Nolan, 2017, Combined immune checkpoint blockade as a therapeutic strategy for BRCA1-mutated breast cancer, Sci. Transl. Med., 9, 10.1126/scitranslmed.aal4922

Wang, 2019, Niraparib activates interferon signaling and potentiates anti-PD-1 antibody efficacy in tumor models, Sci. Rep., 9, 1853, 10.1038/s41598-019-38534-6

Sato, 2017, DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells, Nat. Commun., 8, 1751, 10.1038/s41467-017-01883-9

Lee, 2017, J. Clin. Oncol., 35, 2193, 10.1200/JCO.2016.72.1340

Zhang, 2019, Inhibition of ATM increases interferon signaling and sensitizes pancreatic cancer to immune checkpoint blockade therapy, Cancer Res., 79, 3940, 10.1158/0008-5472.CAN-19-0761

Yi, 2020, ATM mutations benefit bladder cancer patients treated with immune checkpoint inhibitors by acting on the tumor immune microenvironment, Front. Genet., 11, 933, 10.3389/fgene.2020.00933

Sheng, 2020, ATR inhibitor AZD6738 enhances the antitumor activity of radiotherapy and immune checkpoint inhibitors by potentiating the tumor immune microenvironment in hepatocellular carcinoma, J.Immunother.Cancer, 8, 10.1136/jitc-2019-000340

Sun, 2018, Inhibition of ATR downregulates PD-L1 and sensitizes tumor cells to T cell-mediated killing, Am. J. Cancer Res., 8, 1307

Vendetti, 2018, ATR kinase inhibitor AZD6738 potentiates CD8+ T cell-dependent antitumor activity following radiation, J. Clin. Invest., 128, 3926, 10.1172/JCI96519

Lampert, 2020, Clinical outcomes of prexasertib monotherapy in recurrent BRCA wild-type high-grade serous ovarian cancer involve innate and adaptive immune responses, J.Immunother. Cancer, 8, 10.1136/jitc-2019-000516

Sen, 2019, Combination treatment of the oral CHK1 inhibitor, SRA737, and low-dose gemcitabine enhances the effect of programmed death ligand 1 blockade by modulating the immune microenvironment in SCLC, J. Thorac. Oncol., 14, 2152, 10.1016/j.jtho.2019.08.009

Zhang, 2020, CDK7 inhibition potentiates genome instability triggering anti-tumor immunity in small cell lung cancer, Cancer cell, 37, 37, 10.1016/j.ccell.2019.11.003

Sen, 2019, Targeting DNA damage response promotes antitumor immunity through STING-mediated T-cell activation in small cell lung cancer, Cancer discovery, 9, 646, 10.1158/2159-8290.CD-18-1020

Fu, 2015, STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade, Sci. Translat. Med., 7

Thomsen, 2020, The cGAS-STING pathway is a therapeutic target in a preclinical model of hepatocellular carcinoma, Oncogene, 39, 1652, 10.1038/s41388-019-1108-8

Luo, 2017, A STING-activating nanovaccine for cancer immunotherapy, Nat. Nanotechnol., 12, 648, 10.1038/nnano.2017.52

Elion, 2018, Therapeutically active RIG-I agonist induces immunogenic tumor cell killing in breast cancers, Cancer Res., 78, 6183, 10.1158/0008-5472.CAN-18-0730

Westcott, 2021, Mismatch repair deficiency is not sufficient to increase tumor immunogenicity, bioRxiv