Re-education of myeloid immune cells to reduce regulatory T cell expansion and impede breast cancer progression [BMDM_RNA-Seq]
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. Overall design: NR0B2 is known to play an inhibitory role to LXR, one of the major regulators of cholesterol homeostasis, and we had previously demonstrated that NR0B2 functions in myeloid immune cells. Here, murine bone marrow derived macrophages were treated with placebo (DMSO), the NR0B2 agonist DSHN (50µM), the LXR agonist GW3965 (1µM) or a combination of GW3965 and DSHN, for 24h. RNA was isolated. Bulk RNA-seq was performed. Differentially expressed gene profiles between groups were generated