Clariom D gene array of Bone Marrow derived macrophages

Glioblastoma multiforme (GBM) presents a formidable clinical challenge due to its complex microenvironment. Here, we introduce lipid droplet (LD)-loaded macrophages, or tumor-associated foam cells (TAFs), as a previously unidentified immune cell population in GBM. Through extensive analyses of patient tumors, together with in vitro and in vivo investigations, we reveal that TAFs exhibit distinct pro-tumorigenic characteristics related to hypoxia, mesenchymal transition, angiogenesis, and impaired phagocytosis. Moreover, TAF presence correlates with worse patient outcome. Our mechanistic investigations demonstrate that TAF formation is facilitated by lipid cargo from extracellular vesicles released by GBM cells. Importantly, we demonstrate that targeting key enzymes involved in LD formation, such as DGAT1 or ACSL, effectively disrupts TAF functionality. This study establishes TAFs as a prominent immune cell entity in GBM and provides valuable insights into their interplay within the microenvironment. Disruptin 12 samples from patient-derived peripheral blood monocytes, in triplicates, out of which: 3 are hypoxic in vitro differentiated macrophages, 3 are hypoxic in vitro differentiated macrophages treated with DGAT1 inhibitor for 24 hours, 3 are hypoxic in vitro differentiated macrophages treated with GBM-derived EVS, 3 are hypoxic in vitro differentiated macrophages treated with GBM-derived EVs and DGAT1 inhibitor for 24 hours.