Re-education of myeloid immune cells to reduce regulatory T cell expansion and impede breast cancer progression [PyMT_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: The MMTV-PyMT mouse model was crossed with NR0B2+/+ or NR0B2-/- to generate NR0B2+/+ PyMT+ and NR0B2-/- PyMT+ colonies. Tumors were collected and processed for dissociation followed by RNA isolation. Bulk RNA-seq was performed. Differentially expressed genes were determined between tumors from NR0B2+/+ PyMT+ and NR0B2-/- PyMT+