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Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma
Open accessAbstract
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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“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.”
From Microfluidics: A New Tool for Modeling Cancer–Immune Interactions (2016) · cites this paper as [55]
In the citing paper
“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]
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“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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Metadata
- 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
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2010-06-01
- Volume
- 120
- Issue
- 6
- Pages
- 2030-2039
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2877955
- 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
- bronze
- doi.org
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › 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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