Is modulation of immune checkpoints on glioblastoma-infiltrating myeloid cells a viable therapeutic strategy?

Neuro Oncol. 2025 Jan 12;27(1):33-49. doi: 10.1093/neuonc/noae193.

Abstract

The field of immunology has traditionally focused on immune checkpoint modulation of adaptive immune cells. However, many malignancies such as glioblastoma are mostly devoid of T cells and rather are enriched with immunosuppressive myeloid cells of the innate immune system. While some immune checkpoint targets are shared between adaptive and innate immunity, myeloid-specific checkpoints could also serve as potential therapeutics. To better understand the impact of immune checkpoint blockade on myeloid cells, we systematically summarize the current literature focusing on the direct immunological effects of PD-L1/PD-1, CD24/Siglec-10, collagen/LAIR-1, CX3CL1/CX3CR1, and CXCL10/CXCR3. By synthesizing the molecular mechanisms and the translational implications, we aim to prioritize agents in this category of therapeutics for glioblastoma.

Keywords: glioblastoma; immune-checkpoint blockade; myeloid cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / immunology
  • Brain Neoplasms* / pathology
  • Glioblastoma* / drug therapy
  • Glioblastoma* / immunology
  • Glioblastoma* / pathology
  • Humans
  • Immune Checkpoint Inhibitors* / pharmacology
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy* / methods
  • Myeloid Cells* / drug effects
  • Myeloid Cells* / immunology

Substances

  • Immune Checkpoint Inhibitors