Tissue-resident memory CD8+ T cells promote melanoma–immune equilibrium in skin

Tissue-resident memory CD8+ T cells promote melanoma–immune equilibrium in skin.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1038/s41586-018-0812-9
Journal or Publication Title: Nature
Volume: 565
Number: 7739
Page Range: pp. 366-371
Date: 2019
Divisions: Human Viral and Cancer Immunology
Depositing User: General Admin
Identification Number: 10.1038/s41586-018-0812-9
ISSN: 0028-0836
Date Deposited: 15 Dec 2020 01:05
Abstract:

The immune system can suppress tumour development both by eliminating malignant cells and by preventing the outgrowth and spread of cancer cells that resist eradication. Clinical and experimental data suggest that the latter mode of control-termed cancer-immune equilibrium1-can be maintained for prolonged periods of time, possibly up to several decades. Although cancers most frequently originate in epithelial layers, the nature and spatiotemporal dynamics of immune responses that maintain cancer-immune equilibrium in these tissue compartments remain unclear. Here, using a mouse model of transplantable cutaneous melanoma5, we show that tissue-resident memory CD8+ T cells (TRM cells) promote a durable melanoma-immune equilibrium that is confined to the epidermal layer of the skin. A proportion of mice (~40%) transplanted with melanoma cells remained free of macroscopic skin lesions long after epicutaneous inoculation, and generation of tumour-specific epidermal CD69+ CD103+ TRM cells correlated with this spontaneous disease control. By contrast, mice deficient in TRM formation were more susceptible to tumour development. Despite being tumour-free at the macroscopic level, mice frequently harboured melanoma cells in the epidermal layer of the skin long after inoculation, and intravital imaging revealed that these cells were dynamically surveyed by TRM cells. Consistent with their role in melanoma surveillance, tumour-specific TRM cells that were generated before melanoma inoculation conferred profound protection from tumour development independently of recirculating T cells. Finally, depletion of TRM cells triggered tumour outgrowth in a proportion (~20%) of mice with occult melanomas, demonstrating that TRM cells can actively suppress cancer progression. Our results show that TRM cells have a fundamental role in the surveillance of subclinical melanomas in the skin by maintaining cancer-immune equilibrium. As such, they provide strong impetus for exploring these cells as targets of future anticancer immunotherapies.

Creators:
Creators
Email
Park, Simone L.
UNSPECIFIED
Buzzai, Anthony
UNSPECIFIED
Rautela, Jai
UNSPECIFIED
Hor, Jyh Liang
UNSPECIFIED
Hochheiser, Katharina
UNSPECIFIED
Effern, Maike
UNSPECIFIED
McBain, Nathan
UNSPECIFIED
Wagner, Teagan
UNSPECIFIED
Edwards, Jarem
UNSPECIFIED
McConville, Robyn
UNSPECIFIED
Wilmott, James S.
UNSPECIFIED
Scolyer, Richard A.
UNSPECIFIED
Tüting, Thomas
UNSPECIFIED
Palendira, Umaimainthan
UNSPECIFIED
Gyorki, David
UNSPECIFIED
Mueller, Scott N.
UNSPECIFIED
Huntington, Nicholas D.
UNSPECIFIED
Bedoui, Sammy
UNSPECIFIED
Hölzel, Michael
UNSPECIFIED
Mackay, Laura K.
UNSPECIFIED
Waithman, Jason
UNSPECIFIED
Gebhardt, Thomas
UNSPECIFIED
Last Modified: 15 Dec 2020 01:05
URI: https://eprints.centenary.org.au/id/eprint/299

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