Clariom D Pico gene array of microdissected GBM areas or PBMCs.

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 13 samples, out of which: 4 are from microdissected regions high in macrophage marker intensity (2 with high lipid droplet (LD+) and 2 with low lipid droplet (LD-)); and 9 samples are from patient PBMCs (4 monocytes (HC_t0 and P_t0), 2 macrophages (HC_CTRL), and 2 of macrophages plus extracellular vesicles (HC_EVs)). The LD- and HC_CTRL samples are reference/control samples. The brain samples were microdissected from glioblastoma tissues, underwent RNA extraction with AllPrep DNA/RNA Micro Kit for RNA, and hybridization on Affymetrix Clariom Human D Pico microarray cartrige. The PBMCs samples were isolated by CD14+ microbeads, and underwent RNA extraction with AllPrep DNA/RNA Micro Kit for RNA, and hybridization on Affymetrix Clariom Human D Pico microarray cartrige