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

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

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Eyles, Jo, Puaux, Anne-Laure, Wang, Xiaojie, Toh, Benjamin, Prakash, Celine, Hong, Michelle, Tan, Tze Guan, Zheng, Lin, Ong, Lai Chun, Jin, Yi, Kato, Masashi, Prévost-Blondel, Armelle, Chow, Pierce, Yang, Henry, Abastado, Jean-Pierre·2010·Journal of Clinical Investigation

DOI 10.1172/jci42002PMC PMC2877955

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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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Additional file 5 of Local and distant tumor dormancy during early stage breast cancer are associated with the predominance of infiltrating T effector subsets
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Additional file 1 of Local and distant tumor dormancy during early stage breast cancer are associated with the predominance of infiltrating T effector subsets
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Additional file 2 of Local and distant tumor dormancy during early stage breast cancer are associated with the predominance of infiltrating T effector subsets
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Additional file 3 of Local and distant tumor dormancy during early stage breast cancer are associated with the predominance of infiltrating T effector subsets
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Additional file 4 of Local and distant tumor dormancy during early stage breast cancer are associated with the predominance of infiltrating T effector subsets
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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
ORCID: Wang, Xiaojie
Prakash, Celine
Hong, Michelle
Tan, Tze Guan
Zheng, Lin
Jin, Yi
Kato, Masashi
Chow, Pierce
Yang, Henry
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2010-06-01
Volume: 120
Issue: 6
Pages: 2030-2039
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci42002
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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Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma

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