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

ABSTRACT

Introduction: 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:

• Glioblastoma
• GBM
• macrophages
• microglia
• TAM
• targeted therapies
• tumor-associated macrophages
• tumor microenvironment

Acknowledgments

The authors would like to thank Dr Michel Mallat for his fruitful advice and Dr Bertrand for reviewing their work. The research leading to these results has received funding from the program ‘Investissements d’avenir’ ANR-10-IAIHU-06. Institut Universitaire de Cancérologie.

Declaration of interest

A Idbaih reports personal fees from Bristol-Myers Squibb, Hoffman-La Roche, Cipla, and support from Carthera. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.