Re-education of myeloid immune cells to reduce regulatory T cell expansion and impede breast cancer progression [Nanostring]

Due to the limited efficacy of Immune checkpoint blockade (ICB) in mammary solid tumors alternative strategies are required. We demonstrated that cholesterol homeostasis plays a significant role in myeloid immune function and breast cancer progression. In this study, we focus on NR0B2. We conducted both in vitro and in vivo studies along with developing a small molecule agonist. NR0B2 functions within myeloid immune cells as a regulator of the NLRP3 inflammasome, which further facilitates T cell differentiation away from immune-suppressive regulatory T cells (Treg). Furthermore, this signaling pathway was demonstrated to attenuate breast tumor growth and metastasis in mouse models. To understand if NR0B2 plays a role in breast cancer metastasis, we grafted 4T1 cells to Balb/c mice and started treating mice with placebo (DMSO) or NR0B2 agonist (DSHN). Dendritic cells (CD11B+;CD11C+) were isolated from lungs. RNA was isolated. Gene expression profiling analysis was then performed on data obtained from Nanostring. Differentially expressed gene profiles between groups were generate