Cited by 506Cancer Cells and MetastasisCancer Immunotherapy and BiomarkersCancer, Stress, Anesthesia, and Immune Response

Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma

Open access
Eyles, Jo, Puaux, Anne-Laure, Wang, Xiaojie, Toh, Benjamin, Prakash, Celine, Hong, Michelle, Tan, Tze Guan, Zheng, Lin +7 more·2010·Journal of Clinical Investigation

Abstract

Although metastasis is the leading cause of cancer-related death, it is not clear why some patients with localized cancer develop metastatic disease after complete resection of their primary tumor. Such relapses have been attributed to tumor cells that disseminate early and remain dormant for prolonged periods of time; however, little is known about the control of these disseminated tumor cells. Here, we have used a spontaneous mouse model of melanoma to investigate tumor cell dissemination and immune control of metastatic outgrowth. Tumor cells were found to disseminate throughout the body early in development of the primary tumor, even before it became clinically detectable. The disseminated tumor cells remained dormant for varying periods of time depending on the tissue, resulting in staggered metastatic outgrowth. Dormancy in the lung was associated with reduced proliferation of the disseminated tumor cells relative to the primary tumor. This was mediated, at least in part, by cytostatic CD8+ T cells, since depletion of these cells resulted in faster outgrowth of visceral metastases. Our findings predict that immune responses favoring dormancy of disseminated tumor cells, which we propose to be the seed of subsequent macroscopic metastases, are essential for prolonging the survival of early stage cancer patients and suggest that therapeutic strategies designed to reinforce such immune responses may produce marked benefits in these patients.

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Crossref · 10.1172/jci42002

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  • Immune cells can attenuate metastasis.

    “On one hand, there is evidence that immune cells have the capability to attenuate metastasis[54–59], which provides insight into how to restore or enhance their ability to combat cancer.”
  • In a spontaneous mouse melanoma model, dormancy in micrometastatic lesions is mediated by immunosurveillance.

    “studies in a spontaneous mouse melanoma model suggest that dormancy in micrometastatic lesions is mediated by immunosurveillance 131,132”

    From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [132]

  • Cytostatic CD8+ T cells suppress expansion of disseminated tumour cells in the melanoma model.

    “cytostatic CD8 + T cells suppress the expansion of the disseminated tumour cells 132”

    From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [132]

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Research works printed but not linked: 1

  1. [11]11. Bernards R, Weinberg RA. A progression puzzle. Nature. 2002;418(6900):823.

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Authors
Eyles, J., Puaux, A.-L., Wang, X., Toh, B., Prakash, C., Hong, M., Tan, T. G., Zheng, L., Ong, L. C., Jin, Y., Kato, M., Prévost-Blondel, A., Chow, P., Yang, H., & Abastado, J.-P.
Affiliations
  • Agency for Science, Technology and Research (SG)
  • Singapore Immunology Network (SG)
  • SingHealth (SG)
  • Chubu University (JP)
  • National University of Singapore (SG)
Corresponding author
Abastado, Jean-Pierre
Venue
Journal of Clinical Investigation
Published
2010-06-01
Volume
120
Issue
6
Pages
2030-2039
ISSN
0021-9738 (ISSN-L)
OpenAlex
W2063725270
Cited by
506
References
74
Citations by year
2026: 14 · 2025: 18 · 2024: 28 · 2023: 25 · 2022: 31 · 2021: 43 · 2020: 49 · 2019: 29 · 2018: 33 · 2017: 35 · 2016: 36 · 2015: 35 · 2014: 19 · 2013: 36 · 2012: 33
FWCI
17.52
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
Keywords
melanoma, disseminated tumor cells, tumor dormancy, metastasis, immune surveillance, CD8+ T cells, metastatic outgrowth, lung metastasis, visceral metastases
MeSH terms
Animals, Humans, Melanoma, Mice, Transgenic, T-Lymphocytes, Monitoring, Immunologic, Cellular Structures, Mice

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