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Primary breast tumours but not lung metastases induce protective anti-tumour immune responses after Treg-depletion

Hughes, Ellyn, Lauder, Sarah N., Smart, Kathryn, Bloom, Anja, Scott, Jake, Jones, Emma, Somerville, Michelle, Browne, Molly, Blainey, Andrew, Godkin, Andrew ORCID: https://orcid.org/0000-0002-1910-7567, Ager, Ann ORCID: https://orcid.org/0000-0002-5763-8908 and Gallimore, Awen ORCID: https://orcid.org/0000-0001-6675-7004 2020. Primary breast tumours but not lung metastases induce protective anti-tumour immune responses after Treg-depletion. Cancer Immunology, Immunotherapy 69 , 2063 - 2073. 10.1007/s00262-020-02603-x

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Abstract

Although metastatic disease is responsible for the majority of cancer deaths, tests of novel immunotherapies in mouse tumour models often focus on primary tumours without determining whether these therapies also target metastatic disease. This study examined the impact of depleting Foxp3+ regulatory T cells (Treg), on lung metastases, using a mouse model of breast cancer. After Treg-depletion, generation of an immune response to the primary tumour was a critical determinant for limiting development of metastasis. Indeed, resection of the primary tumour abrogated any effect of Treg-depletion on metastases. In addition, whilst the immune response, generated by the primary tumour, prevented metastases development, it had little impact on controlling established disease. Collectively, the data indicate that metastatic cells in the lung are not controlled by immune responses induced by the primary tumour. These findings indicate that targeting Tregs alone will not suffice for treating lung metastases.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Springer Verlag (Germany)
ISSN: 0340-7004
Funders: Cancer Research UK
Date of First Compliant Deposit: 1 June 2020
Date of Acceptance: 12 May 2020
Last Modified: 11 Oct 2023 16:54
URI: https://orca.cardiff.ac.uk/id/eprint/132081

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