Goddard, E. T., Bozic, I., Riddell, S. R. & Ghajar, C. M. Dormant tumour cells, their niches and the influence of immunity. Nat. Cell Biol. 20, 1240–1249 (2018).
Malladi, S. et al. Metastatic latency and immune evasion through autocrine inhibition of WNT. Cell 165, 45–60 (2016).
Pommier, A. et al. Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases. Science 360, eaao4908 (2018).
Pantel, K. et al. Frequent down-regulation of major histocompatibility class I antigen expression on individual micrometastatic carcinoma cells. Cancer Res. 51, 4712–4715 (1991).
Eyles, J. et al. Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma. J. Clin. Invest. 120, 2030–2039 (2010).
Massagué, J. & Ganesh, K. Metastasis-initiating cells and ecosystems. Cancer Discov. 11, 971–994 (2021).
Consonni, D. et al. Lung cancer prognosis before and after recurrence in a population-based setting. JNCI 107, djv059 (2015).
Willis, R. A. The Spread of Tumours in the Human Body (J. & A. Churchill, 1934).
Hadfield, G. The dormant cancer cell. Br. Med. J. 2, 607–610 (1954).
Janni, W. et al. Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse—a European pooled analysis. Clin. Cancer Res. 17, 2967–2976 (2011).
Sosa, M. S., Bragado, P. & Aguirre-Ghiso, J. A. Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat. Rev. Cancer 14, 611–622 (2014).
Xiao, D. et al. Donor cancer transmission in kidney transplantation: a systematic review. Am. J. Transplant. 13, 2645–2652 (2013).
Laughney, A. M. et al. Regenerative lineages and immune-mediated pruning in lung cancer metastasis. Nat. Med. 26, 259–269 (2020).
Winslow, M. M. et al. Suppression of lung adenocarcinoma progression by Nkx2-1. Nature 473, 101–104 (2011).
Marcus, A. et al. Recognition of tumors by the innate immune system and natural killer cells. Adv. Immunol. 122, 91–128 (2014).
McNab, F., Mayer-Barber, K., Sher, A., Wack, A. & O’Garra, A. Type I interferons in infectious disease. Nat. Rev. Immunol. 15, 87–103 (2015).
Kienast, Y. et al. Real-time imaging reveals the single steps of brain metastasis formation. Nat. Med. 16, 116–122 (2010).
Barber, G. N. STING: infection, inflammation and cancer. Nat. Rev. Immunol. 15, 760–770 (2015).
Ablasser, A. & Chen, Z. J. cGAS in action: expanding roles in immunity and inflammation. Science 363, eaat8657 (2019).
Chen, Q. et al. Carcinoma–astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature 533, 493–498 (2016).
Mackenzie, K. J. et al. cGAS surveillance of micronuclei links genome instability to innate immunity. Nature 548, 461–465 (2017).
Bakhoum, S. F. et al. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature 553, 467–472 (2018).
Hong, C. et al. cGAS–STING drives the IL-6-dependent survival of chromosomally instable cancers. Nature 607, 366–373 (2022).
Konno, H., Konno, K. & Barber, G. N. Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling. Cell 155, 688–698 (2013).
Ishikawa, H. & Barber, G. N. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455, 674–678 (2008).
Chen, H. et al. Activation of STAT6 by STING is critical for antiviral innate immunity. Cell 147, 436–446 (2011).
Nguyen, D. X. et al. WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis. Cell 138, 51–62 (2009).
Luis-Ravelo, D. et al. Tumor–stromal interactions of the bone microenvironment: in vitro findings and potential in vivo relevance in metastatic lung cancer models. Clin. Exp. Metastasis 28, 779–791 (2011).
Jeremiah, N. et al. Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J. Clin. Invest. 124, 5516–5520 (2014).
Abe, T. et al. STING recognition of cytoplasmic DNA instigates cellular defense. Mol. Cell 50, 5–15 (2013).
Dufour, J. H. et al. IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J. Immunol. 168, 3195–3204 (2002).
Appay, V. & Rowland-Jones, S. L. RANTES: a versatile and controversial chemokine. Trends Immunol. 22, 83–87 (2001).
Schutyser, E., Struyf, S. & Van Damme, J. The CC chemokine CCL20 and its receptor CCR6. Cytokine Growth Factor Rev. 14, 409–426 (2003).
Kitapma, S. et al. Suppression of STING associated with LKB1 loss in KRAS-driven lung cancer. Cancer Discov. 9, 34–45 (2019).
Bragado, P. et al. TGF-β2 dictates disseminated tumour cell fate in target organs through TGF-β-RIII and p38α/β signalling. Nat. Cell Biol. 15, 1351–1361 (2013).
Ghajar, C. M. et al. The perivascular niche regulates breast tumour dormancy. Nat. Cell Biol. 15, 807–817 (2013).
David, C. J. & Massagué, J. Contextual determinants of TGFβ action in development, immunity and cancer. Nat. Rev. Mol. Cell Biol. 19, 419–435 (2018).
Su, J. et al. TGF-β orchestrates fibrogenic and developmental EMTs via the RAS effector RREB1. Nature 577, 566–571 (2020).
Pan, B. S. et al. An orally available non-nucleotide STING agonist with antitumor activity. Science 369, eaba6098 (2020).
Corrales, L. et al. Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep. 11, 1018–1030 (2015).
Flood, B. A., Higgs, E. F., Li, S. Y., Luke, J. J. & Gajewski, T. F. STING pathway agonism as a cancer therapeutic. Immunol. Rev. 290, 24–38 (2019).
Harding, S. M. et al. Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature 548, 466–470 (2017).
Chen, J. et al. Cell cycle checkpoints cooperate to suppress DNA- and RNA-associated molecular pattern recognition and anti-tumor immune responses. Cell Rep. 32, 108080 (2020).
Deng, L. F. et al. STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 41, 843–852 (2014).
Woo, S. R. et al. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity 41, 830–842 (2014).
Dou, Z. et al. Cytoplasmic chromatin triggers inflammation in senescence and cancer. Nature 550, 402–406 (2017).
Gluck, S. et al. Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence. Nat. Cell Biol. 19, 1061–1070 (2017).
Zierhut, C. et al. The cytoplasmic DNA sensor cGAS promotes mitotic cell death. Cell 178, 302–315.e323 (2019).
Ahn, J. et al. Inflammation-driven carcinogenesis is mediated through STING. Nat. Commun. 5, 5166 (2014).
Vasudevan, A. et al. Single-chromosomal gains can function as metastasis suppressors and promoters in colon cancer. Dev. Cell 52, 413–428.e6 (2020).
Tello-Lafoz, M. et al. Cytotoxic lymphocytes target characteristic biophysical vulnerabilities in cancer. Immunity 54, 1037–1054.e1037 (2021).
DuPage, M., Dooley, A. L. & Jacks, T. Conditional mouse lung cancer models using adenoviral or lentiviral delivery of Cre recombinase. Nat. Protoc. 4, 1064–1072 (2009).
Girardin, S. E. et al. Nod1 detects a unique muropeptide from Gram-negative bacterial peptidoglycan. Science 300, 1584–1587 (2003).
Wang, Q. et al. The E3 ubiquitin ligase AMFR and INSIG1 bridge the activation of TBK1 kinase by modifying the adaptor STING. Immunity 41, 919–933 (2014).
Soto-Feliciano, Y. M. et al. A molecular switch between mammalian MLL complexes dictates response to Menin–MLL inhibition. Cancer Discov. 13, 146–169 (2022).
Doench, J. G. et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR–Cas9. Nat. Biotechnol. 34, 184–191 (2016).
Michlits, G. et al. Multilayered VBC score predicts sgRNAs that efficiently generate loss-of-function alleles. Nat. Methods 17, 708–716 (2020).
Sánchez-Rivera, F. J. et al. A base editing sensor streamlines high-throughput guide validation and engineering of cancer associated variants. Nat. Biotechnol. 40, 862–873 (2022).
Dow, L. E. et al. Inducible in vivo genome editing with CRISPR–Cas9. Nat. Biotechnol. 33, 390–394 (2015).
Minn, A. J. et al. Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J. Clin. Invest. 115, 44–55 (2005).
Ebright, R. Y. et al. Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis. Science 367, 1468–1473 (2020).
Oshimori, N., Oristian, D. & Fuchs, E. TGF-β promotes heterogeneity and drug resistance in squamous cell carcinoma. Cell 160, 963–976 (2015).
Ahn, J., Gutman, D., Saijo, S. & Barber, G. N. STING manifests self DNA-dependent inflammatory disease. Proc. Natl Acad. Sci. USA 109, 19386–19391 (2012).
Setty, M. et al. Characterization of cell fate probabilities in single-cell data with Palantir. Nat. Biotechnol. 37, 451–460 (2019).
McInnes, L., Healy, J. & Melville, J. UMAP: uniform manifold approximation and projection for dimension reduction. Preprint at https://arxiv.org/abs/1802.03426 (2018).
Finak, G. et al. MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data. Genome Biol. 16, 278 (2015).
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
Mootha, V. K. et al. PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267–273 (2003).
Liberzon, A. et al. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst. 1, 417–425 (2015).
Neri, S., Mariani, E., Meneghetti, A., Cattini, L. & Facchini, A. Calcein-acetyoxymethyl cytotoxicity assay: standardization of a method allowing additional analyses on recovered effector cells and supernatants. Clin. Diagn. Lab. Immunol. 8, 1131–1135 (2001).
Chava, S., Bugide, S., Gupta, R. & Wajapeyee, N. Measurement of natural killer cell-mediated cytotoxicity and migration in the context of hepatic tumor cells. J. Vis. Exp. https://doi.org/10.3791/60714 (2020).
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
Karpova, N. N. & Umemori, J. Protocol for methylated DNA immunoprecipitation (MeDIP) analysis. Epigenetic Methods Neurosci. Res. 105, 97–114 (2016).
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