Clariom D gene array of HBMEC cells

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 8 samples from 2 Donors, out of which: 2 are HBMECs that received serum-free conditioned media, 2 are HBMECs that received serum-free conditioned media and LDDDs, 2 are HBMECs that received Evs, and 2 are HBMECs that received Evs and LDDDs.