Primary breast tumours but not lung metastases induce protective anti-tumour immune responses after Treg-depletion
Open Access
- 1 October 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cancer Immunology, Immunotherapy
- Vol. 69 (10), 2063-2073
- https://doi.org/10.1007/s00262-020-02603-x
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.Funding Information
- Tenovus (phd2013/L22)
- Wales Cancer Research Centre
- Cancer Research UK (C16731/A21200)
- Breast Cancer Now (2019DecPR1377)
This publication has 35 references indexed in Scilit:
- Recruitment of monocytes/macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in miceBlood, 2012
- CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasisNature, 2011
- Regulatory T cells in tumor immunityInternational Journal of Cancer, 2010
- Cancer metastasis as a therapeutic targetEuropean Journal of Cancer, 2010
- Antigen Specificity Determines the Pro- or Antitumoral Nature of CD8+ T CellsThe Journal of Immunology, 2009
- Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1The Journal of Experimental Medicine, 2009
- Metastatic Cancer CellAnnual review of pathology, 2008
- Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like diseaseThe Journal of Experimental Medicine, 2007
- Mouse 4T1 Breast Tumor ModelCurrent Protocols in Immunology, 2000
- Defective presentation to class I-restricted cytotoxic T lymphocytes in vaccinia-infected cells is overcome by enhanced degradation of antigen.The Journal of Experimental Medicine, 1988