Control of tumor growth by TSLP during colorectal cancer

Abstract

Abstract Thymic stromal lymphopoietin (TSLP) is a cytokine involved in promoting tumor growth during breast and pancreatic cancer by promoting Th2 cell-mediated inflammation. Despite being essential to maintain Treg cell homeostasis in the mouse and human intestine, a role for TSLP in colorectal cancer has never been shown. To determine if TSLP affects tumor growth during colorectal cancer, we utilized a murine model of colitis-associated colorectal cancer. TSLP deficient mice exhibited decreased tumor numbers when compared to the WT littermate controls. Moreover, we found that tumors in TSLP−/− mice were also significantly smaller in size than WT mouse tumors. TSLP was mainly localized in the tumor tissue, indicating that it might be produced by cancer or cancer-associated cells. Further, TSLP receptor (TSLPR) expression was significantly upregulated after development of cancer. To determine if TSLP signals directly on the tumor cells, we utilized Villincre TSLPRflox mice in which the TSLPR expression is absent only in intestinal epithelial cells (IECs). Consistent with the TSLP−/− mice, lack of TSLP signaling on IECs led to a decrease in tumor number as well as tumor size, suggesting that TSLP signals directly on the IECs to promote tumor growth. Overall, these data show a novel role for TSLP in controlling tumor progression during colorectal cancer and identify it as a potential target for immunotherapy intervention.