Genome instability and crosstalk with the immune response

Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.

Article  PubMed  CAS  Google Scholar 

Chabanon RM, Rouanne M, Lord CJ, Soria J-C, Pasero P, Postel-Vinay S. Targeting the DNA damage response in immuno-oncology: developments and opportunities. Nat Rev Cancer. 2021;21:701–17.

Article  PubMed  CAS  Google Scholar 

Kornepati AVR, Rogers CM, Sung P, Curiel TJ. The complementarity of DDR, nucleic acids and anti-tumour immunity. Nature. 2023;619:475–86.

Article  PubMed  CAS  Google Scholar 

Samson N, Ablasser A. The cGAS-STING pathway and cancer. Nat Cancer. 2022;3:1452–63.

Article  PubMed  CAS  Google Scholar 

Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–20.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–13.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Marabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, Nakagawa K, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020;21:1353–65.

Article  PubMed  CAS  Google Scholar 

Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, et al. PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer. N Engl J Med. 2022;386:2363–76.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Mi M, Ye C, Yuan Y. Neoadjuvant PD-1 blockade: a promising nonoperative strategy for mismatch repair-deficient, locally advanced rectal cancer. Signal Transduct Target Ther. 2022;7:361.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Chen G, Jin Y, Guan W-L, Zhang R-X, Xiao W-W, Cai P-Q, et al. Neoadjuvant PD-1 blockade with sintilimab in mismatch-repair deficient, locally advanced rectal cancer: an open-label, single-centre phase 2 study. Lancet Gastroenterol Hepatol. 2023;8:422–31.

Article  PubMed  CAS  Google Scholar 

U.S. Food and Drug Administration. FDA approves pembrolizumab for adults and children with TMB-H solid tumors. FDA official website. 2020; Available from: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors. Cited 2024 Apr 26.

Zhao P, Li L, Jiang X, Li Q. Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy. J Hematol Oncol. 2019;12:54.

Article  PubMed  PubMed Central  Google Scholar 

Guan J, Lu C, Jin Q, Chen ZJ, Guan J, Lu C, et al. MLH1 Deficiency-Triggered DNA Hyperexcision by Exonuclease 1 Activates the cGAS-STING Pathway. Cancer Cell. 2021;39:109-121.e5.

Article  PubMed  CAS  Google Scholar 

Lu C, Guan J, Lu S, Diaz LA, Lu C, Guan J, et al. DNA sensing in mismatch repair-deficient tumor cells is essential for anti-tumor immunity. Cancer Cell. 2021;39:96-108.e6.

Article  PubMed  CAS  Google Scholar 

Chabanon RM, Muirhead G, Krastev DB, Adam J, Morel D, Garrido M, et al. PARP inhibition enhances tumor cell–intrinsic immunity in ERCC1-deficient non–small cell lung cancer. J Clin Investig. 2019;129:1211–28.

Article  PubMed  PubMed Central  Google Scholar 

Danlos F-X, Texier M, Job B, Mouraud S, Cassard L, Baldini C, et al. Genomic Instability and protumoral inflammation are associated with primary resistance to Anti-PD-1 + antiangiogenesis in malignant pleural mesothelioma. Cancer Discov. 2023;13:858–79.

Article  PubMed  PubMed Central  Google Scholar 

Bakhoum SF, Ngo B, Laughney AM, Cavallo JA, Murphy CJ, Ly P, et al. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature. 2018;553:467–72.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Bakhoum SF, Cantley LC. The multifaceted role of chromosomal instability in cancer and its microenvironment. Cell. 2018;174:1–27.

Article  Google Scholar 

Crow YJ, Leitch A, Hayward BE, Garner A, Parmar R, Griffith E, et al. Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection. Nat Genet. 2006;38:910–6.

Article  PubMed  CAS  Google Scholar 

Cristini A, Groh M, Kristiansen MS, Gromak N. RNA/DNA Hybrid Interactome Identifies DXH9 as a Molecular Player in Transcriptional Termination and R-Loop-Associated DNA Damage. Cell Rep. 2018;23:1891–905.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Coquel F, Silva MJ, Técher H, Zadorozhny K, Sharma S, Nieminuszczy J, et al. SAMHD1 acts at stalled replication forks to prevent interferon induction. Nature. 2018;557:57–61.

Article  PubMed  CAS  Google Scholar 

Daddacha W, Koyen AE, Bastien AJ, Head PSE, Dhere VR, Nabeta GN, et al. SAMHD1 Promotes DNA End Resection to Facilitate DNA Repair by Homologous Recombination. Cell Rep. 2017;20:1921–35.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Zhang B, Li Y, Zhang J, Wang Y, Liang C, Lu T, et al. ADAR1 links R-loop homeostasis to ATR activation in replication stress response. Nucleic Acids Res. 2023;51:11668–87.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Park K, Ryoo J, Jeong H, Kim M, Lee S, Hwang S-Y, et al. Aicardi-Goutières syndrome-associated gene SAMHD1 preserves genome integrity by preventing R-loop formation at transcription-replication conflict regions. PLoS Genet. 2021;17: e1009523.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Pizzi S, Sertic S, Orcesi S, Cereda C, Bianchi M, Jackson AP, et al. Reduction of hRNase H2 activity in Aicardi-Goutières syndrome cells leads to replication stress and genome instability. Hum Mol Genet. 2015;24:649–58.

Article  PubMed  CAS  Google Scholar 

Hiller B, Achleitner M, Glage S, Naumann R, Behrendt R, Roers A. Mammalian RNase H2 removes ribonucleotides from DNA to maintain genome integrity. J Exp Med. 2012;209:1419–26.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Aditi null, Downing SM, Schreiner PA, Kwak YD, Li Y, Shaw TI, et al. Genome instability independent of type I interferon signaling drives neuropathology caused by impaired ribonucleotide excision repair. Neuron. 2021;109:3962–3979.

Crow YJ, Manel N. Aicardi-Goutières syndrome and the type I interferonopathies. Nat Rev Immunol. 2015;15:429–40.

Article  PubMed  CAS  Google Scholar 

Sprenger H-G, MacVicar T, Bahat A, Fiedler KU, Hermans S, Ehrentraut D, et al. Cellular pyrimidine imbalance triggers mitochondrial DNA-dependent innate immunity. Nat Metab. 2021;3:636–50.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Donne R, Saroul-Ainama M, Cordier P, Hammoutene A, Kabore C, Stadler M, et al. Replication stress triggered by nucleotide pool imbalance drives DNA damage and cGAS-STING pathway activation in NAFLD. Dev Cell. 2022;57:1728-1741.e6.

Article  PubMed  CAS  Google Scholar 

Chen M, Yu S, van der Sluis T, Zwager MC, Schröder CP, van der Vegt B, et al. cGAS-STING pathway expression correlates with genomic instability and immune cell infiltration in breast cancer. NPJ Breast Cancer. 2024;10:1.

Comments (0)

No login
gif