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

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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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          Author and article information

          Journal
          J Clin Invest
          The Journal of clinical investigation
          American Society for Clinical Investigation
          1558-8238
          0021-9738
          Jun 2010
          : 120
          : 6
          Affiliations
          [1 ] Singapore Immunology Network, BMSI, A-STAR, Singapore.
          Article
          42002
          10.1172/JCI42002
          2877955
          20501944
          8f282496-83a4-4e5a-8f74-808d89c0af14
          History

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