Hughes and Lauder et al. used the 4T1 mouse breast cancer model to examine the impact of relief from immune suppression by Treg depletion on lung metastatic disease in the presence or absence of the primary breast tumor. Treg depletion in 4T1 tumor-bearing mice resulted in primary tumor regression and decreased lung metastases (mets), dependent on control of the primary tumor. However, if the primary tumor was surgically removed prior to Treg depletion, there was no effect on lung mets. The studies suggest the primary tumor and lung mets respond differently to Treg depletion, and additional approaches may be required to control metastatic growth.
Contributed by Katherine Turner
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.