Lack of Functional TSLP Receptors Mitigates Th2 Polarization and the Establishment and Growth of 4T1 Primary Breast Tumours but has Different Effects on Tumour Quantities in the Lung and Brain

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Abstract

The 4T1 mammary carcinoma cell line produces TSLP. We had hypothesized that TSLP promotes the development of a permissive environment for the growth and metastasis of primary tumour and that this is associated with a Th2-polarized antitumour immune response. We found that, in Tslpr−/− mice, the mean tumour diameters were smaller from days 27 to 40, and relatively fewer tumour cells were present in the lung, compared with wild-type mice. Polarization of the Th2 cytokine profile was also diminished in Tslpr−/− mice. These findings confirmed those reported previously by others. Here, we further show that primary tumours are established less often in Tslpr−/− mice and that, unexpectedly, the relative number of tumour cells in the brain is greater in Tslpr−/− mice compared with wild-type mice. Findings from our cytotoxicity assays show that 4T1-directed lysis is undetectable in both WT and Tslpr−/− mice, ruling out the possibility that altered cytotoxic responses in Tslpr−/− mice are responsible for the differences we observed. In a human tissue microarray, positive staining for TSLP was seen in tumour cells from breast cancer tissue, but it was also seen in normal glandular epithelial cells from normal breast tissue, which has not been shown before. Thus, our findings provide new insight into the effects of TSLP in metastatic breast cancer.

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