Abstract
Tumour cells migrate very early from primary sites to distant sites, and yet metastases often take years to manifest themselves clinically or never even surface within a patient’s lifetime. This pause in cancer progression emphasizes the existence of barriers that constrain the growth of disseminated tumour cells (DTCs) at distant sites. Although the nature of these barriers to metastasis might include DTC-intrinsic traits, recent studies have established that the local microenvironment also controls the formation of metastases. In this Perspective, I discuss how site-specific differences of the immune system might be a major selective growth restraint on DTCs, and argue that harnessing tissue immunity will be essential for the next stage in immunotherapy development that reliably prevents the establishment of metastases.
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Acknowledgements
The author apologizes to those whose invaluable contributions to the field were not cited owing to space limitations. The author is grateful to J. C. Guimaraes and F. Landum for their helpful comments on the manuscript. The author’s laboratory is supported by the Champalimaud Foundation, the Beug Foundation (2021 Metastasis Research Prize) and the European Molecular Biology Organization (EMBO Installation Grant 5329).
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Glossary
- Dormancy
-
A state of pause in cancer progression in which individual disseminated tumour cells are quiescent and reversibly arrested in G0 phase of the cell cycle.
- Disseminated tumour cells
-
(DTCs). Cancer cells that have left the primary tumour and survived in the circulation to land in a distant site.
- Metastases
-
Outgrowths of disseminated tumour cells that are histologically or radiologically detectable.
- Niche
-
A term borrowed from ecology that refers to a unique and optimal tissue microenvironment with defined nurturing and positional cues in a given anatomical location that allows a cell or a group of cells to survive and function.
- Pre-metastatic niche
-
A microenvironment within a distant site that is permissive for the survival and outgrowth of incoming disseminated tumour cells before their arrival at that site.
- Tissue-resident immune cells
-
Immune cells that occupy tissues for prolonged periods and undergo little or no recirculation.
- Tolerogenic milieu
-
An environment readily suppressive of adaptive immune responses, promoting tolerance to frequently encountered antigens, while maintaining local and systemic homeostasis.
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Correia, A.L. Locally sourced: site-specific immune barriers to metastasis. Nat Rev Immunol 23, 522–538 (2023). https://doi.org/10.1038/s41577-023-00836-2
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DOI: https://doi.org/10.1038/s41577-023-00836-2
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