Senescent macrophages in tumor: phenotypes, roles, and interventions

Cell Death Dis. 2025 Oct 6;16(1):677. doi: 10.1038/s41419-025-08000-5.

Abstract

The senescence of immune cells, including macrophages, that accompany the initiation and development of tumors has become a novel research hotspot. Recently, studies have reported the molecular characteristics of senescent macrophages (sMACs) in the tumor microenvironment (TME), including cell cycle arrest, senescence-associated secretory phenotype (SASP), and senescence-associated β-galactosidase phenotype (SA-β-gal), and these characteristics not only suggest that sMACs are functionally rich in the TME, but also have the potential to become biomarkers for the identification of sMACs. The in-depth study and analysis of sMACs dialogue and mediating the changes of signaling pathways related to tumor and immune cells will help us to better understand the balance between tumor and aging. Here, we review recent advances in sMACs, including phenotypical molecular characteristics, potential functions and intervention approaches.

Publication types

  • Review

MeSH terms

  • Animals
  • Cellular Senescence*
  • Humans
  • Macrophages* / immunology
  • Macrophages* / metabolism
  • Macrophages* / pathology
  • Neoplasms* / immunology
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Phenotype
  • Senescence-Associated Secretory Phenotype
  • Signal Transduction
  • Tumor Microenvironment