The role of TSLP in modulating the anti-tumor immune response in a mouse model of metastatic breast cancer
Thymic stromal lymphopoietin (TSLP) is produced primarily but not exclusively by epithelial cells. It has been shown to induce the production of Th2 cytokines and inflammation in allergic disease. Since Th2 cytokines have been shown to be detrimental to the anti-tumor immune response, we hypothesized that TSLP promotes the development of a permissive microenvironment for breast cancer, which facilitates the growth and metastasis of primary tumors and that it does so, in part, by inducing the development of a Th2-mediated immune response. Using the 4T1 mouse breast cancer model, we used wild type (WT) and TSLP receptor deficient (TSLPR-/-) mice to compare primary tumor growth, metastasis to the lungs and brain, cytokine profiles and 4T1-directed lysis. Some of these parameters were also examined in mice treated with an anti-TSLP neutralizing antibody. We showed that in TSLPR-/- mice, primary tumor establishment, growth and metastasis to the lungs were reduced, compared to WT mice. Unexpectedly, we observed that metastasis to the brain was increased. When mice were treated with anti-TSLP neutralizing antibody, the only significant effect that we observed was a reduction in metastasis to the lung in WT mice. We also studied TSLP expression in a human invasive breast cancer microarray (TMA). Both the normal breast epithelial cells and breast cancer cells stained positively for TSLP, but it appears that it might be more highly expressed in the breast cancer tissue. Taken together, our data support the hypothesis that TSLP promotes the development of a permissive microenvironment for breast cancer. However, the role of TSLP appears to be complex since the absence of TSLP responsiveness resulted in a greater level of metastasis to the brain.
immunology, cancer, pathology