Thymic stromal lymphopoietin mediates breast cancer progression and metastasis (48.9)

Abstract

Abstract Breast cancer escape and metastasis is an active process that requires inflammation and participation of immune cells. We have previously reported that this is a primary tumor-controlled process which activates lungs to produce CCL17 and CCL22 to facilitate lung metastasis together with the recruitment of CCR4+ regulatory T cells (Tregs). To understand the mechanism of this process, we performed expression array analysis in both metastatic and non-metastatic cancer cells and found that metastatic cells produced thymic stromal lymphopoietin (TSLP), an IL-7-like type 1 inflammatory cytokine that is often associated with the induction of Th2-type allergic responses in the lungs. Moreover, TSLP was also abundantly expressed in variety of human solid tumors, including breast, lung, colon and ovarian cancers. To gain further insights into the role of TSLP in cancer progression, we have blocked TSLP expression in cancer cells and found that TSLP is required for efficient breast cancer escape and metastasis. Moreover, utilizing adoptive transfer studies in TSLPR deficient mice, we demonstrated that by targeting CD4+ T cells to induce Th2-type inflammatory responses, cancer-produced TSLP promoted cancer escape. Taken together, our data indicate that TSLP is an important factor that needs to be controlled to effectively combat with cancer escape.