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Metastasis

Finding the needle in the haystack

Nature Reviews Cancer volume 24, page 163 (2024)Cite this article

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Targeting dormant disseminated tumour cells (DTCs) with immunotherapies holds promise to prevent metastatic recurrence. However, little is known about the mechanisms by which DTCs escape immune surveillance. Goddard, Linde et al. now find that the relative scarcity of DTCs protects them from anti-tumour immunity.

The authors next characterized transcriptomes and measured protein abundance of solitary DTCs, micro-metastases and macro-metastases isolated from mouse lungs and found that DTCs, when compared to metastases, downregulate major histocompatibility complex class I (MHC-I). Interestingly, downregulation of MHC-I was independent of the cell cycle status of DTCs and of the immune pressure, as MHC-I reduction also occurred in immune-compromised mice. Although this suggested that DTCs evade T cell recognition by downregulation of MHC-I, the authors found that the extent of MHC-I reduction in single DTCs is not sufficient to evade immune recognition by T cells, indicating that other mechanisms are at play.

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Original article

  • Goddard, E. T. et al. Immune evasion of dormant disseminated tumor cells is due to their scarcity and can be overcome by T cell immunotherapies. Cancer Cell 42, 119–134.e12 (2024)

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  1. Nature Reviews Cancer http://www.nature.com/nrc/

    Daniela Senft

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  1. Daniela Senft
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Correspondence to Daniela Senft.

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Senft, D. Finding the needle in the haystack. Nat Rev Cancer 24, 163 (2024). https://doi.org/10.1038/s41568-024-00673-y

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  • DOI: https://doi.org/10.1038/s41568-024-00673-y

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