Brain Tumor Microenvironment and Host State: Implications for Immunotherapy.

Published online

Journal Article (Review)

Glioblastoma (GBM) is a highly lethal brain tumor with poor responses to immunotherapies that have been successful in more immunogenic cancers with less immunosuppressive tumor microenvironments (TME). The GBM TME is uniquely challenging to treat due to tumor cell-extrinsic components that are native to the brain, as well as tumor-intrinsic mechanisms that aid in immune evasion. Lowering the barrier of immunosuppression by targeting the genetically stable tumor stroma presents opportunities to treat the tumor in a way that circumvents the complications of targeting a constantly mutating tumor with tumor antigen-directed therapies. Tumor-associated monocytes, macrophages, and microglia are a stromal element of particular interest. Macrophages and monocytes compose the bulk of infiltrating immune cells and are considered to have protumor and immunosuppressive effects. Targeting these cells or other stromal elements is expected to convert what is considered the "cold" TME of GBM to a more "hot" TME phenotype. This conversion could increase the effectiveness of what have become conventional frontline immunotherapies in GBM-creating opportunities for better treatment through combination therapy.

Full Text

Duke Authors

Cited Authors

  • Tomaszewski, W; Sanchez-Perez, L; Gajewski, TF; Sampson, JH

Published Date

  • February 25, 2019

Published In

PubMed ID

  • 30804019

Pubmed Central ID

  • 30804019

International Standard Serial Number (ISSN)

  • 1078-0432

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-18-1627

Language

  • eng

Conference Location

  • United States