Understanding the glioblastoma immune microenvironment as basis for the development of new immunotherapeutic strategies

Elife. 2020 Feb 4:9:e52176. doi: 10.7554/eLife.52176.

Abstract

Cancer immunotherapy by immune checkpoint blockade has proven its great potential by saving the lives of a proportion of late stage patients with immunogenic tumor types. However, even in these sensitive tumor types, the majority of patients do not sufficiently respond to the therapy. Furthermore, other tumor types, including glioblastoma, remain largely refractory. The glioblastoma immune microenvironment is recognized as highly immunosuppressive, posing a major hurdle for inducing immune-mediated destruction of cancer cells. Scattered information is available about the presence and activity of immunosuppressive or immunostimulatory cell types in glioblastoma tumors, including tumor-associated macrophages, tumor-infiltrating dendritic cells and regulatory T cells. These cell types are heterogeneous at the level of ontogeny, spatial distribution and functionality within the tumor immune compartment, providing insight in the complex cellular and molecular interplay that determines the immune refractory state in glioblastoma. This knowledge may also yield next generation molecular targets for therapeutic intervention.

Keywords: cancer biology; glioblastoma; immunotherapy; microenvironment; regulatory T cell; tumor-associated dendritic cell; tumor-associated macrophage.

Publication types

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

MeSH terms

  • Brain / cytology
  • Brain / immunology
  • Brain / metabolism
  • Brain Neoplasms* / immunology
  • Brain Neoplasms* / therapy
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Glioblastoma* / immunology
  • Glioblastoma* / therapy
  • Humans
  • Immunotherapy*
  • Macrophages / cytology
  • Macrophages / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Microenvironment / immunology*

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.