Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation
Ruochen Du,
Shashwat Tripathi,
Hinda Najem,
Daniel J. Brat,
Rimas V. Lukas,
Peng Zhang,
Amy B. Heimberger
Affiliations
Ruochen Du
Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Shashwat Tripathi
Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Hinda Najem
Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Daniel J. Brat
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Rimas V. Lukas
Malnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Peng Zhang
Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Amy B. Heimberger
Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Macrophages and microglia are professional phagocytes that sense and migrate toward “eat-me” signals. The role of phagocytic cells is to maintain homeostasis by engulfing senescent or apoptotic cells, debris, and abnormally aggregated macromolecules. Usually, dying cells send out “find-me” signals, facilitating the recruitment of phagocytes. Healthy cells can also promote or inhibit the phagocytosis phenomenon of macrophages and microglia by tuning the balance between “eat-me” and “don’t-eat-me” signals at different stages in their lifespan, while the “don’t-eat-me” signals are often hijacked by tumor cells as a mechanism of immune evasion. Using a combination of bioinformatic analysis and spatial profiling, we delineate the balance of the “don’t-eat-me” CD47/SIRPα and “eat-me” CALR/STC1 ligand–receptor interactions to guide therapeutic strategies that are being developed for glioblastoma sequestered in the central nervous system (CNS).
