Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation

Cells. 2024 May 11;13(10):823. doi: 10.3390/cells13100823.

Abstract

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).

Keywords: gliomas; immune checkpoint blockade; myeloid cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Differentiation
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • CD47 Antigen* / metabolism
  • Calreticulin* / metabolism
  • Cell Death
  • Glioblastoma* / metabolism
  • Glioblastoma* / pathology
  • Glioblastoma* / therapy
  • Humans
  • Macrophages / immunology
  • Macrophages / metabolism
  • Microglia / metabolism
  • Microglia / pathology
  • Phagocytes* / metabolism
  • Phagocytosis*
  • Receptors, Immunologic / metabolism

Substances

  • CD47 Antigen
  • Calreticulin
  • Receptors, Immunologic
  • CALR protein, human
  • SIRPA protein, human
  • CD47 protein, human
  • Antigens, Differentiation