Targeting immune checkpoints on myeloid cells: current status and future directions

Cancer Immunol Immunother. 2025 Jan 3;74(2):40. doi: 10.1007/s00262-024-03856-6.

Abstract

Myeloid cells accumulate extensively in most tumors and play a critical role in immunosuppression of the tumor microenvironment (TME). Like T cells, myeloid cells also express immune checkpoint molecules, which induce the immunosuppressive phenotype of these cells. In this review, we summarize the tumor-promoting function and immune checkpoint expression of four types of myeloid cells: macrophages, neutrophils, dendritic cells, and myeloid-derived suppressor cells, which are the main components of the TME. By summarizing the research status of myeloid checkpoints, we propose that blocking immune checkpoints on myeloid cells might be an effective strategy to reverse the immunosuppressive status of the TME. Moreover, combining nanotechnology, cellular therapy, and bispecific antibodies to achieve precise targeting of myeloid immune checkpoints can help to avoid the adverse effects of systemic administration, ultimately achieving a balance between efficacy and safety in cancer therapy.

Keywords: Immune checkpoint; Myeloid cells; Nanotherapy; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immune Checkpoint Proteins / metabolism
  • Immunotherapy / methods
  • Myeloid Cells* / immunology
  • Neoplasms* / immunology
  • Neoplasms* / therapy
  • Tumor Microenvironment* / immunology

Substances

  • Immune Checkpoint Inhibitors
  • Immune Checkpoint Proteins