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Emerging roles of regulatory T cells in tumour progression and metastasis

  • Non-Thematic Review
  • Published:
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Abstract

The metastasis of cancer is a complex and life-threatening process that is only partially understood. Immune suppressive cells are recognized as important contributors to tumour progression and may also promote the development and growth of tumour metastases. Specifically, regulatory T cells (Tregs) have been found to promote primary tumour progression, and emerging pre-clinical data suggests that Tregs may promote metastasis and metastatic tumour growth. While the precise role that Tregs play in metastatic progression is understudied, recent findings have indicated that by suppressing innate and adaptive anti-tumour immunity, Tregs may shield tumour cells from immune detection, and thereby allow tumour cells to survive, proliferate and acquire characteristics that facilitate dissemination. This review will highlight our current understanding of Tregs in metastasis, including an overview of pre-clinical findings and discussion of clinical data regarding Tregs and therapeutic outcome. Evolving strategies to directly ablate Tregs or to inhibit their function will also be discussed. Improving our understanding of how Tregs may influence tumour metastasis may lead to novel treatments for metastatic cancer.

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Abbreviations

Tregs:

Regulatory T cells

pTregs:

Peripheral regulatory T cells

tTregs:

Thymic regulatory T cells

Foxp3:

Forkhead box P3

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Acknowledgments

This work was supported by the Canadian Institutes of Health Research (Grant MOP-126138) and the BC Cancer Foundation. E.C.H. is supported by a Frederick Banting and Charles Best Canada Graduate Scholarship from the Canadian Institutes of Health Research and by a 4-year doctoral fellowship from the University of British Columbia. K.L.B. is a Michael Smith Foundation for Health Research Biomedical Research scholar.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Integrative Oncology, British Columbia Cancer Agency, 10-108, 675 West 10th Avenue, Vancouver, British Columbia, V5Z 1L3, Canada

    Kevin L. Bennewith

  2. Interdisciplinary Oncology Program, University of British Columbia, Vancouver, British Columbia, Canada

    Elizabeth C. Halvorsen & Kevin L. Bennewith

  3. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada

    Sahar M. Mahmoud & Kevin L. Bennewith

  4. Department of Integrative Oncology, British Columbia Cancer Agency, 9-202, 675 West 10th Avenue, Vancouver, British Columbia, V5Z 1L3, Canada

    Elizabeth C. Halvorsen & Sahar M. Mahmoud

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  1. Elizabeth C. Halvorsen
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Halvorsen, E.C., Mahmoud, S.M. & Bennewith, K.L. Emerging roles of regulatory T cells in tumour progression and metastasis. Cancer Metastasis Rev 33, 1025–1041 (2014). https://doi.org/10.1007/s10555-014-9529-x

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