Despite increased focus on the clinical relevance of dormant metastatic disease, our understanding of dormant niches, mechanisms underlying emergence from dormancy, and the immune system’s role in this phenomenon, remains in its infancy. Here, we discuss key work that has shaped our current understanding of these topics. Because tumour dormancy provides a unique therapeutic window to prevent metastatic disease, we discuss on-going clinical trials and weigh the potential for immunotherapy to eradicate dormant disease.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Cancer and Metastasis Reviews Open Access 09 February 2023
Cancer and Metastasis Reviews Open Access 04 January 2023
Scientific Reports Open Access 10 June 2022
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Early Breast Cancer Trialists’ Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365, 1687–1717 (2005).
Thomsen, F. B. et al. Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer: long-term follow-up of the SPCG-6 study. Eur. J. Cancer 51, 1283–1292 (2015).
Scher, H. I. et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N. Engl. J. Med 367, 1187–1197 (2012).
Pan, H. et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N. Engl. J. Med. 377, 1836–1846 (2017).
Goss, P. E. & Chambers, A. F. Does tumour dormancy offer a therapeutic target? Nat. Rev. Cancer 10, 871–877 (2010).
Naumov, G. N. et al. Persistence of solitary mammary carcinoma cells in a secondary site: a possible contributor to dormancy. Cancer Res. 62, 2162–2168 (2002).
Aguirre-Ghiso, J. A. Models, mechanisms and clinical evidence for cancer dormancy. Nat. Rev. Cancer 7, 834–846 (2007).
Gimbrone, M. A. Jr., Leapman, S. B., Cotran, R. S. & Folkman, J. Tumor dormancy in vivo by prevention of neovascularization. J. Exp. Med. 136, 261–276 (1972).
Folkman, J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 285, 1182–1186 (1971).
Rakhra, K. et al. CD4+ T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. Cancer Cell 18, 485–498 (2010).
Ghajar, C. M. Metastasis prevention by targeting the dormant niche. Nat. Rev. Cancer 15, 238–247 (2015).
Klein, G. Foulds’ dangerous idea revisited: the multistep development of tumors 40 years later. Adv. Cancer Res. 72, 1–23 (1998).
Collins, V. P., Loeffler, R. K. & Tivey, H. Observations on growth rates of human tumors. Amer. J. Roentgenol. Ra. 76, 988–1000 (1956).
Klein, C. A. Parallel progression of primary tumours and metastases. Nat. Rev. Cancer 9, 302–312 (2009).
Harper, K. L. et al. Mechanism of early dissemination and metastasis in Her2+ mammary cancer. Nature 540, 588–592 (2016).
Hosseini, H. et al. Early dissemination seeds metastasis in breast cancer. Nature 540, 552–558 (2016).
Gruber, I. V. et al. Relationship between hematogenous tumor cell dissemination and cellular immunity in DCIS patients. Anticancer Res. 36, 2345–2351 (2016).
Sanger, N. et al. Disseminated tumor cells in the bone marrow of patients with ductal carcinoma in situ. Int. J. Cancer 129, 2522–2526 (2011).
Morgan, T. M. et al. Disseminated tumor cells in prostate cancer patients after radical prostatectomy and without evidence of disease predicts biochemical recurrence. Clin. Cancer Res. 15, 677–683 (2009).
Husemann, Y. et al. Systemic spread is an early step in breast cancer. Cancer Cell 13, 58–68 (2008).
Schlimok, G. et al. Micrometastatic cancer cells in bone marrow: in vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies. Proc. Natl Acad. Sci. USA 84, 8672–8676 (1987).
Stoecklein, N. H. et al. Direct genetic analysis of single disseminated cancer cells for prediction of outcome and therapy selection in esophageal cancer. Cancer Cell 13, 441–453 (2008).
Schardt, J. A. et al. Genomic analysis of single cytokeratin-positive cells from bone marrow reveals early mutational events in breast cancer. Cancer Cell 8, 227–239 (2005).
Schmidt-Kittler, O. et al. From latent disseminated cells to overt metastasis: genetic analysis of systemic breast cancer progression. Proc. Natl Acad. Sci. USA 100, 7737–7742 (2003).
Brastianos, P. K. et al. Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets. Cancer Discov. 5, 1164–1177 (2015).
Becker, T. E. et al. The genomic heritage of lymph node metastases: implications for clinical management of patients with breast cancer. Ann. Surg. Oncol. 15, 1056–1063 (2008).
Bissig, H. et al. Evaluation of the clonal relationship between primary and metastatic renal cell carcinoma by comparative genomic hybridization. Am. J. Pathol. 155, 267–274 (1999).
Kuukasjarvi, T. et al. Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer. Cancer Res. 57, 1597–1604 (1997).
Jones, S. et al. Comparative lesion sequencing provides insights into tumor evolution. Proc. Natl Acad. Sci. USA 105, 4283–4288 (2008).
Yachida, S. et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467, 1114–1117 (2010).
Kumar, A. et al. Substantial interindividual and limited intraindividual genomic diversity among tumors from men with metastatic prostate cancer. Nat. Med. 22, 369–378 (2016).
Pantel, K. et al. Immunocytological detection of bone marrow micrometastasis in operable non-small cell lung cancer. Cancer Res. 53, 1027–1031 (1993).
Woelfle, U. et al. Bi-specific immunomagnetic enrichment of micrometastatic tumour cell clusters from bone marrow of cancer patients. J. Immunol. Methods 300, 136–145 (2005).
Pantel, K. et al. Frequency and prognostic significance of isolated tumour cells in bone marrow of patients with non-small-cell lung cancer without overt metastases. Lancet 347, 649–653 (1996).
Kiel, M. J. et al. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121, 1109–1121 (2005).
Butler, J. M. et al. Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells. Cell Stem Cell 6, 251–264 (2010).
Chen, J. Y. et al. Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche. Nature 530, 223–227 (2016).
Kienast, Y. et al. Real-time imaging reveals the single steps of brain metastasis formation. Nat. Med. 16, 116–122 (2010).
Cao, Z. et al. Angiocrine factors deployed by tumor vascular niche induce B cell lymphoma invasiveness and chemoresistance. Cancer Cell 25, 350–365 (2014).
Cao, Z. et al. Molecular checkpoint decisions made by subverted vascular niche transform indolent tumor cells into chemoresistant cancer stem cells. Cancer Cell 31, 110–126 (2017).
Price, T. T. et al. Dormant breast cancer micrometastases reside in specific bone marrow niches that regulate their transit to and from bone. Sci. Transl. Med. 8, 340ra373 (2016).
Ghajar, C. M. et al. The perivascular niche regulates breast tumour dormancy. Nat. Cell Biol. 15, 807–817 (2013).
Tamplin, O. J. et al. Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular niche. Cell 160, 241–252 (2015).
Shiozawa, Y. et al. Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J. Clin. Invest. 121, 1298–1312 (2011).
Butler, J. M., Kobayashi, H. & Rafii, S. Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors. Nat. Rev. Cancer 10, 138–146 (2010).
Scadden, D. T. Nice neighborhood: emerging concepts of the stem cell niche. Cell 157, 41–50 (2014).
Bragado, P., Sosa, M. S., Keely, P., Condeelis, J. & Aguirre-Ghiso, J. A. Microenvironments dictating tumor cell dormancy. Recent Res. Cancer 195, 25–39 (2012).
Katayama, Y. et al. PSGL-1 participates in E-selectin-mediated progenitor homing to bone marrow: evidence for cooperation between E-selectin ligands and alpha4 integrin. Blood 102, 2060–2067 (2003).
Sugiyama, T., Kohara, H., Noda, M. & Nagasawa, T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25, 977–988 (2006).
Fischer, J. C. et al. Diagnostic leukapheresis enables reliable detection of circulating tumor cells of nonmetastatic cancer patients. Proc. Natl Acad. Sci. USA 110, 16580–16585 (2013).
Wei, Q. & Frenette, P. S. Niches for hematopoietic stem cells and their progeny. Immunity 48, 632–648 (2018).
Rafii, S., Butler, J. M. & Ding, B. S. Angiocrine functions of organ-specific endothelial cells. Nature 529, 316–325 (2016).
Gao, H. et al. The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites. Cell 150, 764–779 (2012).
Shiozawa, Y. et al. GAS6/AXL axis regulates prostate cancer invasion, proliferation, and survival in the bone marrow niche. Neoplasia 12, 116–127 (2010).
Taichman, R. S. et al. GAS6 receptor status is associated with dormancy and bone metastatic tumor formation. PLoS ONE 8, e61873 (2013).
Yumoto, K. et al. Axl is required for TGF-beta2-induced dormancy of prostate cancer cells in the bone marrow. Sci. Rep. 6, 36520 (2016).
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).
Kobayashi, A. et al. Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone. J. Exp. Med. 208, 2641–2655 (2011).
Catena, R. et al. Bone marrow-derived Gr1+ cells can generate a metastasis-resistant microenvironment via induced secretion of thrombospondin-1. Cancer Discov. 3, 578–589 (2013).
Johnson, R. W. et al. Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow. Nat. Cell Biol. 18, 1078–1089 (2016).
Lawson, M. A. et al. Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche. Nat. Commun. 6, 8983 (2015).
Wang, H. et al. The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells. Cancer Cell 27, 193–210 (2015).
Nash, K. T. et al. Requirement of KISS1 secretion for multiple organ metastasis suppression and maintenance of tumor dormancy. J. Natl Cancer Inst. 99, 309–321 (2007).
Aguirre Ghiso, J. A., Kovalski, K. & Ossowski, L. Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. J. Cell Biol. 147, 89–104 (1999).
Aguirre-Ghiso, J. A., Liu, D., Mignatti, A., Kovalski, K. & Ossowski, L. Urokinase receptor and fibronectin regulate the ERK(MAPK) to p38(MAPK) activity ratios that determine carcinoma cell proliferation or dormancy in vivo. Mol. Biol. Cell 12, 863–879 (2001).
Aguirre-Ghiso, J. A., Estrada, Y., Liu, D. & Ossowski, L. ERK(MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK). Cancer Res. 63, 1684–1695 (2003).
Ranganathan, A. C., Adam, A. P. & Aguirre-Ghiso, J. A. Opposing roles of mitogenic and stress signaling pathways in the induction of cancer dormancy. Cell Cycle 5, 1799–1807 (2006).
Palmieri, D. et al. Medroxyprogesterone acetate elevation of Nm23-H1 metastasis suppressor expression in hormone receptor-negative breast cancer. J. Natl Cancer Inst. 97, 632–642 (2005)
Hartsough, M. T. et al. Nm23-H1 metastasis suppressor phosphorylation of kinase suppressor of Ras via a histidine protein kinase pathway. J. Biol. Chem. 277, 32389–32399 (2002).
Hickson, J. A. et al. The p38 kinases MKK4 and MKK6 suppress metastatic colonization in human ovarian carcinoma. Cancer Res. 66, 2264–2270 (2006).
Gawrzak, S. et al. MSK1 regulates luminal cell differentiation and metastatic dormancy in ER+ breast cancer. Nat. Cell Biol. 20, 211–221 (2018).
Kennecke, H. et al. Metastatic behavior of breast cancer subtypes. J. Clin. Oncol. 28, 3271–3277 (2010).
Weaver, V. M. et al. Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies. J. Cell Biol. 137, 231–245 (1997).
Wang, F. et al. Reciprocal interactions between beta1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: a different perspective in epithelial biology. Proc. Natl Acad. Sci. USA 95, 14821–14826 (1998).
Wang, F. et al. Phenotypic reversion or death of cancer cells by altering signaling pathways in three-dimensional contexts. J. Natl Cancer Inst. 94, 1494–1503 (2002).
Beliveau, A. et al. Raf-induced MMP9 disrupts tissue architecture of human breast cells in three-dimensional culture and is necessary for tumor growth in vivo. Genes Dev. 24, 2800–2811 (2010).
Kaplan, R. N. et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438, 820–827 (2005).
Peinado, H. et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat. Med. 18, 883–891 (2012).
Costa-Silva, B. et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat. Cell Biol. 17, 816–826 (2015).
Hoshino, A. et al. Tumour exosome integrins determine organotropic metastasis. Nature 527, 329–335 (2015).
Erler, J. T. et al. Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 15, 35–44 (2009).
Murgai, M. et al. KLF4-dependent perivascular cell plasticity mediates pre-metastatic niche formation and metastasis. Nat. Med. 23, 1176–1190 (2017).
Barkan, D. et al. Metastatic growth from dormant cells induced by a col-I-enriched fibrotic environment. Cancer Res. 70, 5706–5716 (2010).
Cox, T. R. et al. LOX-mediated collagen crosslinking is responsible for fibrosis-enhanced metastasis. Cancer Res. 73, 1721–1732 (2013).
Goddard, E. T. et al. The rodent liver undergoes weaning-induced involution and supports breast cancer metastasis. Cancer Discov. 7, 177–187 (2017).
Quail, D. F. et al. Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF. Nat. Cell Biol. 19, 974–987 (2017).
Malanchi, I. et al. Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 481, 85–89 (2012).
Oskarsson, T. et al. Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat. Med. 17, 867–874 (2011).
O’Connell, J. T. et al. VEGF-A and Tenascin-C produced by S100A4+ stromal cells are important for metastatic colonization. Proc. Natl Acad. Sci. USA 108, 16002–16007 (2011).
Hiratsuka, S., Watanabe, A., Aburatani, H. & Maru, Y. Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat. Cell Biol. 8, 1369–1375 (2006).
O’Reilly, M. S. et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88, 277–285 (1997).
O’Reilly, M. S. et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79, 315–328 (1994).
Rachman-Tzemah, C. et al. Blocking surgically induced lysyl oxidase activity reduces the risk of lung metastases. Cell Rep. 19, 774–784 (2017).
Retsky, M. et al. Reduction of breast cancer relapses with perioperative non-steroidal anti-inflammatory drugs: new findings and a review. Curr. Med. Chem. 20, 4163–4176 (2013).
Gangloff, S. et al. Quiescence unveils a novel mutational force in fission yeast. eLife 6, e27469 (2017).
Hacohen, N., Fritsch, E. F., Carter, T. A., Lander, E. S. & Wu, C. J. Getting personal with neoantigen-based therapeutic cancer vaccines. Cancer Immunol. Res. 1, 11–15 (2013).
Rosenberg, S. A. & Restifo, N. P. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 348, 62–68 (2015).
Sharma, P. & Allison, J. P. The future of immune checkpoint therapy. Science 348, 56–61 (2015).
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).
Agudo, J. et al. Quiescent tissue stem cells evade immune surveillance. Immunity 48, 271–285 (2018).
Hirata, Y. et al. CD150high bone marrow Tregs maintain hematopoietic stem cell quiescence and immune privilege via adenosine. Cell Stem Cell 22, 445–453 e445 (2018).
Bichsel, C. A. et al. Increased PD-L1 expression and IL-6 secretion characterize human lung tumor-derived perivascular-like cells that promote vascular leakage in a perfusable microvasculature model. Sci. Rep. 7, 10636 (2017).
Schmittnaegel, M. et al. Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade. Sci. Transl. Med. 9, eaak9670 (2017).
Hirosue, S. et al. Steady-state antigen scavenging, cross-presentation, and CD8+ T cell priming: a new role for lymphatic endothelial cells. J. Immunol. 192, 5002–5011 (2014).
Dieterich, L. C. et al. Tumor-associated lymphatic vessels upregulate PDL1 to inhibit T-cell activation. Front. Immunol. 8, 66 (2017).
Schietinger, A. et al. Tumor-specific T cell dysfunction is a dynamic antigen-driven differentiation program initiated early during tumorigenesis. Immunity 45, 389–401 (2016).
Koebel, C. M. et al. Adaptive immunity maintains occult cancer in an equilibrium state. Nature 450, 903–907 (2007).
Teng, M. W. et al. Opposing roles for IL-23 and IL-12 in maintaining occult cancer in an equilibrium state. Cancer Res 72, 3987–3996 (2012).
Farrar, J. D. et al. Cancer dormancy. VII. A regulatory role for CD8+ T cells and IFN-γ in establishing and maintaining the tumor-dormant state. J. Immunol. 162, 2842–2849 (1999).
Muller, M. et al. EblacZ tumor dormancy in bone marrow and lymph nodes: active control of proliferating tumor cells by CD8+ immune T cells. Cancer Res. 58, 5439–5446 (1998).
Mahnke, Y. D., Schwendemann, J., Beckhove, P. & Schirrmacher, V. Maintenance of long-term tumour-specific T-cell memory by residual dormant tumour cells. Immunology 115, 325–336 (2005).
Shankaran, V. et al. IFN-γ and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410, 1107–1111 (2001).
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).
Malladi, S. et al. Metastatic latency and immune evasion through autocrine inhibition of WNT. Cell 165, 45–60 (2016).
Moini, M., Schilsky, M. L. & Tichy, E. M. Review on immunosuppression in liver transplantation. World J. Hepatol. 7, 1355–1368 (2015).
Cimino, F. M. & Snyder, K. A. Primary care of the solid organ transplant recipient. Am. Fam. Physician 93, 203–210 (2016).
Buell, J. F. et al. Donor transmitted malignancies. Ann. Transplant 9, 53–56 (2004).
Strauss, D. C. & Thomas, J. M. Transmission of donor melanoma by organ transplantation. Lancet Oncol. 11, 790–796 (2010).
Xiao, D. et al. Donor cancer transmission in kidney transplantation: a systematic review. Am. J Transplant 13, 2645–2652 (2013).
Jimsheleishvili, S. et al. Extracranial glioblastoma in transplant recipients. J. Cancer Res. Clin. Oncol. 140, 801–807 (2014).
Diaz, L. A. Jr. et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 486, 537–540 (2012).
Davies, C. et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 381, 805–816 (2013).
Naume, B. et al. Clinical outcome with correlation to disseminated tumor cell (DTC) status after DTC-guided secondary adjuvant treatment with docetaxel in early breast cancer. J. Clin. Oncol. 32, 3848–3857 (2014).
Braun, S. et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N. Engl. J. Med. 353, 793–802 (2005).
Filipits, M. et al. The PAM50 risk-of-recurrence score predicts risk for late distant recurrence after endocrine therapy in postmenopausal women with endocrine-responsive early breast cancer. Clin. Cancer Res. 20, 1298–1305 (2014).
Sparano, J. A. et al. Circulating tumor cells (CTCs) five years after diagnosis are prognostic for late recurrence in operable stage II-III breast cancer. Cancer Res. 78, Abstract GS6–03 (2018).
Sadelain, M., Riviere, I. & Riddell, S. Therapeutic T cell engineering. Nature 545, 423–431 (2017).
June, C. H., O’Connor, R. S., Kawalekar, O. U., Ghassemi, S. & Milone, M. C. CAR T cell immunotherapy for human cancer. Science 359, 1361–1365 (2018).
Zhang, Q. et al. Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity. Nat. Immunol. 19, 723–732 (2018).
Mehta, R. S. & Rezvani, K. Chimeric antigen receptor expressing natural killer cells for the immunotherapy of cancer. Front Immunol. 9, 283 (2018).
Smith, T. T. et al. In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers. Nat. Nanotechnol. 12, 813–820 (2017).
Graef, P. et al. Serial transfer of single-cell-derived immunocompetence reveals stemness of CD8+ central memory T cells. Immunity 41, 116–126 (2014).
Gattinoni, L. et al. Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells. J. Clin. Invest. 115, 1616–1626 (2005).
Berger, C. et al. Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. J. Clin. Invest. 118, 294–305 (2008).
Turtle, C. J. et al. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J. Clin. Invest. 126, 2123–2138 (2016).
Silberstein, L. et al. Proximity-based differential single-cell analysis of the niche to identify stem/progenitor cell regulators. Cell Stem Cell 19, 530–543 (2016).
Fredericks, D. N. & Relman, D. A. Sequence-based identification of microbial pathogens: a reconsideration of Koch’s postulates. Clin. Microbiol. Rev. 9, 18–33 (1996).
Cote, R. J., Rosen, P. P., Lesser, M. L., Old, L. J. & Osborne, M. P. Prediction of early relapse in patients with operable breast cancer by detection of occult bone marrow micrometastases. J. Clin. Oncol. 9, 1749–1756 (1991).
Lindemann, F., Schlimok, G., Dirschedl, P., Witte, J. & Riethmuller, G. Prognostic significance of micrometastatic tumour cells in bone marrow of colorectal cancer patients. Lancet 340, 685–689 (1992).
Mansi, J. L. et al. Bone marrow micrometastases in primary breast cancer: prognostic significance after 6 years’ follow-up. Eur. J. Cancer 27, 1552–1555 (1991).
Schlimok, G. et al. Micrometastatic tumour cells in bone marrow of patients with gastric cancer: methodological aspects of detection and prognostic significance. Eur. J. Cancer 27, 1461–1465 (1991).
Thorban, S. et al. Immunocytochemical detection of disseminated tumor cells in the bone marrow of patients with esophageal carcinoma. J. Natl Cancer Inst. 88, 1222–1227 (1996).
Putz, E. et al. Phenotypic characteristics of cell lines derived from disseminated cancer cells in bone marrow of patients with solid epithelial tumors: establishment of working models for human micrometastases. Cancer Res. 59, 241–248 (1999).
Suzuki, M., Mose, E. S., Montel, V. & Tarin, D. Dormant cancer cells retrieved from metastasis-free organs regain tumorigenic and metastatic potency. Am. J. Pathol. 169, 673–681 (2006).
Klein, C. A. Selection and adaptation during metastatic cancer progression. Nature 501, 365–372 (2013).
S.R.R. is funded in part by the NIH/NCI (R01 CA114536). C.M.G. is funded by the National Breast Cancer Coalition’s Artemis Project, an Era of Hope Award from the United States Department of Defence Breast Cancer Research Program (W841XWH-15-1-0201), the Breast Cancer Research Foundation (IIDRP-17-001), the W.M. Keck Foundation and the NIH/NCI (U54CA193461-01).
The authors declare no competing interests.
Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Goddard, E.T., Bozic, I., Riddell, S.R. et al. Dormant tumour cells, their niches and the influence of immunity. Nat Cell Biol 20, 1240–1249 (2018). https://doi.org/10.1038/s41556-018-0214-0
This article is cited by
KISS1 metastasis suppressor in tumor dormancy: a potential therapeutic target for metastatic cancers?
Cancer and Metastasis Reviews (2023)
Cancer and Metastasis Reviews (2023)
Cancer and Metastasis Reviews (2023)
Cancer and Metastasis Reviews (2023)