LC3-associated phagocytosis of neutrophils triggers tumor ferroptotic cell death in glioblastoma

(Figure presented.) Neutrophils induce ferroptosis in glioblastoma, thus promoting necrosis during early tumor progression but the underlying mechanisms remain unclear. Here, neutrophil engulfment by tumor cells is uncovered as a critical step facilitating the transfer of neutrophilic granules and tumor cell ferroptosis. Statins inhibit neutrophil-induced tumor cell death by blocking neutrophilic granule transfer. Integrin-mediated cell adhesion is required for tumor cell killing by neutrophils. Neutrophils are engulfed by tumor cells before releasing myeloperoxidase-containing contents into tumor cells. LC3-associated phagocytosis is responsible for neutrophil internalization by tumor cells. Myeloperoxidase inhibition or Vps34 depletion reduces necrosis in glioblastomas and prolongs survival of tumor-bearing mice.