The Dynamics of Interactions Among Immune and Glioblastoma Cells

Neuromolecular Med. 2015 Dec;17(4):335-52. doi: 10.1007/s12017-015-8362-x. Epub 2015 Jul 30.

Abstract

Glioblastoma is the most common intracranial malignancy that constitutes about 50 % of all gliomas. Despite aggressive, multimodal therapy consisting of surgery, radiation, and chemotherapy, the outcome of patients with glioblastoma remains poor with 5-year survival rates of <10 %. Resistance to conventional therapies is most likely caused by several factors. Alterations in the functions of local immune mediators may represent a critical contributor to this resistance. The tumor microenvironment contains innate and adaptive immune cells in addition to the cancer cells and their surrounding stroma. These various cells communicate with each other by means of direct cell-cell contact or by soluble factors including cytokines and chemokines, and act in autocrine and paracrine manners to modulate tumor growth. There are dynamic interactions among the local immune elements and the tumor cells, where primarily the protective immune cells attempt to overcome the malignant cells. However, by developing somatic mutations and epigenetic modifications, the glioblastoma tumor cells acquire the capability of counteracting the local immune responses, and even exploit the immune cells and products for their own growth benefits. In this review, we survey those immune mechanisms that likely contribute to glioblastoma pathogenesis and may serve as a basis for novel treatment strategies.

Keywords: Glioblastoma; Immune cells; Immune-based therapeutic strategies; Immunology; Tumor infiltration.

Publication types

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

MeSH terms

  • Blood-Brain Barrier
  • Brain Neoplasms / genetics
  • Brain Neoplasms / immunology
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / therapy
  • Cancer Vaccines / therapeutic use
  • Cell Communication
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Epigenesis, Genetic
  • Extracellular Vesicles
  • Glioblastoma / genetics
  • Glioblastoma / immunology
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Glioblastoma / therapy
  • Humans
  • Immunotherapy / methods
  • Inflammation
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Macrophages / pathology*
  • Microglia / pathology*
  • Mutation
  • Myeloid Cells / pathology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplastic Stem Cells / pathology
  • Transforming Growth Factor beta / metabolism
  • Tumor Escape / immunology*
  • Tumor Microenvironment*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Cancer Vaccines
  • Cytokines
  • Neoplasm Proteins
  • Transforming Growth Factor beta
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A