Exploring thymic stromal lymphopoietin in the breast cancer microenvironment: A preliminary study.

Abstract

Cancer participates in the immune response by releasing several factors, such as cytokines and chemokines, which can alter the ability of the immune system to identify and eradicate cancer. Notably, the role of thymic stromal lymphopoietin (TSLP) in breast cancer (BC) is currently controversial and unclear. The present study characterized the role of TSLP in BC and its interaction with peripheral blood mononuclear cells, focusing on the CD14⁺CD16⁺ monocyte population via the secretome released by BC cells. The UALCAN and Gene Expression Profiling Interactive Analysis tools were employed to define TSLP expression in BC, and its levels in different BC subtype cell lines were validated using reverse transcription-quantitative PCR and ELISA. In addition, TIMER 2.0 was used to determine the abundance of immune cell infiltration in BC. Subsequently, the effects of BC conditioned medium (CM) and TSLP were investigated on CD14⁺CD16⁺ monocytes via flow cytometry. A Cellular Reactive Oxygen Species (ROS) Assay Kit, Fluo-4 AM assay and ATPlite assay were used to explore the effects of TSLP on monocyte cellular metabolism. The results showed that a reduction in TSLP expression was associated with an unfavorable prognosis in BC. Furthermore, a higher expression of TSLP in CM from a non-tumoral cell line increased the percentage of CD14⁺CD16⁺ monocytes. Finally, it was revealed that TSLP decreased intracellular ATP levels, while increasing intracellular calcium levels and producing ROS in THP-1 cells. Therefore, TSLP may be considered a novel biomarker in the BC microenvironment, where it could regulate cellular metabolism through the expansion of CD14⁺CD16⁺ monocytes.