Interactions between tumor-associated macrophages and tumor cells in glioblastoma: unraveling promising targeted therapies

Expert Rev Neurother. 2018 Sep;18(9):729-737. doi: 10.1080/14737175.2018.1510321. Epub 2018 Aug 22.

Abstract

Glioblastoma (GBM) is the deadliest primary malignant central nervous system (CNS) tumor with a median overall survival of 15 months despite a very intensive therapeutic regimen including maximal safe surgery, radiotherapy, and chemotherapy. Therefore, GBM treatment still raises major biological and therapeutic challenges. Areas covered: One of the hallmarks of the GBM is its tumor microenvironment including tumor-associated macrophages (TAM). TAM, accounting for approximately 30% of the GBM bulk cell population, may explain, at least in part, the immunosuppressive features of GBMs. The TAM are active and highly plastic immune cells and include two major ontogenetically different cell populations: (i) microglia and, (ii) monocytes-derived macrophages (MDM). TAM recruited to the tumor bulk can be reprogramed by GBM cells resulting in an ineffective anti-tumor response. Interestingly, interactions between TAM and GBM cells promote tumor oncogenesis (i.e. tumor cells proliferation and migration/invasion). This review aims to explore TAM targeting in GBM as a promising therapeutic option in the near future. Expert Commentary: A better understanding of TAM-GBM interactions and dynamics will certainly uncover new anti-GBM therapeutic avenues.

Keywords: GBM; Glioblastoma; TAM; macrophages; microglia; targeted therapies; tumor microenvironment; tumor-associated macrophages.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain Neoplasms / pathology*
  • Brain Neoplasms / therapy
  • Glioblastoma / pathology*
  • Glioblastoma / therapy
  • Humans
  • Macrophages / pathology*
  • Microglia / pathology