Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.
Google ScholarÂ
Heemskerk B, Kvistborg P, Schumacher TN. The cancer antigenome. Embo J. 2013;32:194–203.
Google ScholarÂ
Maleki Vareki S. High and low mutational burden tumors versus immunologically hot and cold tumors and response to immune checkpoint inhibitors. J Immunother Cancer. 2018;6:157.
Google ScholarÂ
Tang H, Wang Y, Chlewicki LK, Zhang Y, Guo J, Liang W, et al. Facilitating T cell infiltration in tumor microenvironment overcomes resistance to PD-L1 blockade. Cancer Cell. 2016;29:285–96.
Google ScholarÂ
Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515:568–71.
Google ScholarÂ
Bortolomeazzi M, Keddar MR, Montorsi L, Acha-Sagredo A, Benedetti L, Temelkovski D, et al. Immunogenomics of colorectal cancer response to checkpoint blockade: analysis of the KEYNOTE 177 trial and validation cohorts. Gastroenterology. 2021;161:1179–93.
Google ScholarÂ
Li A, Yi M, Qin S, Song Y, Chu Q, Wu K. Activating cGAS-STING pathway for the optimal effect of cancer immunotherapy. J Hematol Oncol. 2019;12:35.
Google ScholarÂ
Urban-Wojciuk Z, Khan MM, Oyler BL, FÃ¥hraeus R, Marek-Trzonkowska N, Nita-Lazar A, et al. The role of TLRs in anti-cancer immunity and tumor rejection. Front Immunol. 2019;10:2388.
Google ScholarÂ
Mills KH. TLR-dependent T cell activation in autoimmunity. Nat Rev Immunol. 2011;11:807–22.
Google ScholarÂ
Ramanjulu JM, Pesiridis GS, Yang J, Concha N, Singhaus R, Zhang SY, et al. Design of amidobenzimidazole STING receptor agonists with systemic activity. Nature. 2018;564:439–43.
Google ScholarÂ
Xu N, Palmer DC, Robeson AC, Shou P, Bommiasamy H, Laurie SJ, et al. STING agonist promotes CAR T cell trafficking and persistence in breast cancer. J Exp Med. 2021;218:e20200844.
Margolis SR, Wilson SC, Vance RE. Evolutionary origins of cGAS-STING signaling. Trends Immunol. 2017;38:733–43.
Google ScholarÂ
Ng KW, Marshall EA, Bell JC, Lam WL. cGAS-STING and cancer: dichotomous roles in tumor immunity and development. Trends Immunol. 2018;39:44–54.
Google ScholarÂ
Motwani M, Pesiridis S, Fitzgerald KA. DNA sensing by the cGAS-STING pathway in health and disease. Nat Rev Genet. 2019;20:657–74.
Google ScholarÂ
Tao J, Zhou X, Jiang Z. cGAS-cGAMP-STING: the three musketeers of cytosolic DNA sensing and signaling. IUBMB life. 2016;68:858–70.
Google ScholarÂ
Klinakis A, Karagiannis D, Rampias T. Targeting DNA repair in cancer: current state and novel approaches. Cell Mol Life Sci. 2020;77:677–703.
Google ScholarÂ
Uyanik B, Grigorash BB, Goloudina AR, Demidov ON. DNA damage-induced phosphatase Wip1 in regulation of hematopoiesis, immune system and inflammation. Cell Death Discov. 2017;3:17018.
Google ScholarÂ
Harding SM, Benci JL, Irianto J, Discher DE, Minn AJ, Greenberg RA. Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature. 2017;548:466–70.
Google ScholarÂ
Mackenzie KJ, Carroll P, Martin CA, Murina O, Fluteau A, Simpson DJ, et al. cGAS surveillance of micronuclei links genome instability to innate immunity. Nature. 2017;548:461–5.
Google ScholarÂ
Chen M, Wang W, Hu S, Tong Y, Li Y, Wei Q, et al. Co-targeting WIP1 and PARP induces synthetic lethality in hepatocellular carcinoma. Cell Commun Signal. 2022;20:39.
Google ScholarÂ
Cha H, Lowe JM, Li H, Lee JS, Belova GI, Bulavin DV, et al. Wip1 directly dephosphorylates gamma-H2AX and attenuates the DNA damage response. Cancer Res. 2010;70:4112–22.
Google ScholarÂ
DeNardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL, Madden SF, et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov. 2011;1:54–67.
Google ScholarÂ
Lee PY, Li Y, Kumagai Y, Xu Y, Weinstein JS, Kellner ES, et al. Type I interferon modulates monocyte recruitment and maturation in chronic inflammation. Am J Pathol. 2009;175:2023–33.
Google ScholarÂ
Ma W, Oliveira-Nunes MC, Xu K, Kossenkov A, Reiner BC, Crist RC, et al. Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment. Nat Commun. 2023;14:2632.
Google ScholarÂ
Zhang Q, Green MD, Lang X, Lazarus J, Parsels JD, Wei S, et al. Inhibition of ATM increases interferon signaling and sensitizes pancreatic cancer to immune checkpoint blockade therapy. Cancer Res. 2019;79:3940–51.
Google ScholarÂ
Guan J, Lu C, Jin Q, Lu H, Chen X, Tian L, et al. MLH1 deficiency-triggered DNA hyperexcision by exonuclease 1 activates the cGAS-STING pathway. Cancer cell. 2020;39:109–121.
Seo J, Kim SC, Lee HS, Kim JK, Shon HJ, Salleh NL, et al. Genome-wide profiles of H2AX and gamma-H2AX differentiate endogenous and exogenous DNA damage hotspots in human cells. Nucleic Acids Res. 2012;40:5965–74.
Google ScholarÂ
Bose D. cGAS/STING pathway in cancer: Jekyll and Hyde story of cancer immune response. Int J Mol Sci. 2017;18:2456.
Parkes EE, Walker SM, Taggart LE, McCabe N, Knight LA, Wilkinson R, et al. Activation of STING-dependent innate immune signaling by S-phase-specific DNA damage in breast cancer. J Natl Cancer Inst. 2017;109:djw199.
Araujo JM, Gomez AC, Aguilar A, Salgado R, Balko JM, Bravo L, et al. Effect of CCL5 expression in the recruitment of immune cells in triple negative breast cancer. Sci Rep. 2018;8:4899.
Google ScholarÂ
Mulligan AM, Raitman I, Feeley L, Pinnaduwage D, Nguyen LT, O’Malley FP, et al. Tumoral lymphocytic infiltration and expression of the chemokine CXCL10 in breast cancers from the Ontario Familial Breast Cancer Registry. Clin Cancer Res. 2013;19:336–46.
Google ScholarÂ
Lugrin J, Martinon F. The AIM2 inflammasome: sensor of pathogens and cellular perturbations. Immunol Rev. 2018;281:99–114.
Unterholzner L, Keating SE, Baran M, Horan KA, Jensen SB, Sharma S, et al. IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol. 2010;11:997–1004.
Zhao Y, Liang L, Fan Y, Sun S, An L, Shi Z, et al. PPM1B negatively regulates antiviral response via dephosphorylating TBK1. Cell Signal. 2012;24:2197–204.
Google ScholarÂ
Xiang W, Zhang Q, Lin X, Wu S, Zhou Y, Meng F, et al. PPM1A silences cytosolic RNA sensing and antiviral defense through direct dephosphorylation of MAVS and TBK1. Sci Adv. 2016;2:e1501889.
Google ScholarÂ
Li Z, Liu G, Sun L, Teng Y, Guo X, Jia J, et al. PPM1A regulates antiviral signaling by antagonizing TBK1-mediated STING phosphorylation and aggregation. PLoS Pathog. 2015;11:e1004783.
Google ScholarÂ
Garcia-Diaz A, Shin DS, Moreno BH, Saco J, Escuin-Ordinas H, Rodriguez GA, et al. Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression. Cell Rep. 2017;19:1189–201.
Google ScholarÂ
André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med. 2020;383:2207–18.
Google ScholarÂ
Le DT, Kim TW, Van Cutsem E, Geva R, Jager D, Hara H, et al. Phase II open-label study of pembrolizumab in treatment-refractory, microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: KEYNOTE-164. J Clin Oncol. 2020;38:11–9.
Google ScholarÂ
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.
Google ScholarÂ
Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18:1182–91.
Google ScholarÂ
Wei B, Xu L, Guo W, Wang Y, Wu J, Li X, et al. SHP2-mediated inhibition of DNA repair contributes to cGAS-STING activation and chemotherapeutic sensitivity in colon cancer. Cancer Res. 2021;81:3215–28.
Google ScholarÂ
Lu C, Guan J, Lu S, Jin Q, Rousseau B, Lu T, et al. DNA sensing in mismatch repair-deficient tumor cells is essential for anti-tumor immunity. Cancer Cell. 2021;39:96–108.e6.
Google ScholarÂ
Moon SH, Nguyen TA, Darlington Y, Lu X, Donehower LA. Dephosphorylation of gamma-H2AX by WIP1: an important homeostatic regulatory event in DNA repair and cell cycle control. Cell Cycle. 2010;9:2092–6.
Google ScholarÂ
Shreeram S, Demidov ON, Hee WK, Yamaguchi H, Onishi N, Kek C, et al. Wip1 phosphatase modulates ATM-dependent signaling pathways. Mol Cell. 2006;23:757–64.
Google ScholarÂ
Fujimoto H, Onishi N, Kato N, Takekawa M, Xu XZ, Kosugi A, et al. Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase. Cell Death Differ. 2006;13:1170–80.
Google ScholarÂ
Sun L, Wu J, Du F, Chen X, Chen ZJ. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science. 2013;339:786–91.
Google ScholarÂ
Corrales L, McWhirter SM, Dubensky TW Jr., Gajewski TF. The host STING pathway at the interface of cancer and immunity. J Clin Invest. 2016;126:2404–11.
Google ScholarÂ
Almine JF, O’Hare CA, Dunphy G, Haga IR, Naik RJ, Atrih A, et al. IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes. Nat Commun. 2017;8:14392.
Google ScholarÂ
Jameson MB, Thompson PI, Baguley BC, Evans BD, Harvey VJ, Porter DJ, et al. Clinical aspects of a phase I trial of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a novel antivascular agent. Br J Cancer. 2003;88:1844–50.
Google ScholarÂ
Lara PN Jr, Douillard JY, Nakagawa K, von Pawel J, McKeage MJ, Albert I, et al. Randomized phase III placebo-controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent vadimezan (ASA404) in advanced non-small-cell lung cancer. J Clin Oncol. 2011;29:2965–71.
Google ScholarÂ
Sen T, Rodriguez BL, Chen L, Corte CMD, Morikawa N, Fujimoto J, et al. Targeting DNA damage response promotes antitumor immunity through STING-mediated T-cell activation in small cell lung cancer. Cancer Discov. 2019;9:646–61.
Google ScholarÂ
Liang Y, Tang H, Guo J, Qiu X, Yang Z, Ren Z, et al. Targeting IFNalpha to tumor by anti-PD-L1 creates feedforward antitumor responses to overcome checkpoint blockade resistance. Nat Commun. 2018;9:4586.
Google ScholarÂ
Benci JL, Xu B, Qiu Y, Wu TJ, Dada H, Twyman-Saint Victor C, et al. Tumor interferon signaling regulates a multigenic resistance program to immune checkpoint blockade. Cell. 2016;167:1540–54.e12.
Google ScholarÂ
Benci JL, Johnson LR, Choa R, Xu Y, Qiu J, Zhou Z, et al. Opposing functions of interferon coordinate adaptive and innate immune responses to cancer immune checkpoint blockade. Cell. 2019;178:933–48.e14.
Google ScholarÂ

