The Potential for Genetically Altered Microglia to Influence Glioma Treatment

Abstract

Diffuse and unstoppable infiltration of brain and spinal cord tissue by neoplastic glial cells is the single most important therapeutic problem posed by the common glioma group of tumors: astrocytoma, oligoastrocytoma, oligodendroglioma, their malignant variants and glioblastoma. These neoplasms account for more than two thirds of all malignant central nervous system tumors. However, most glioma research focuses on an examination of the tumor cells rather than on host-specific, tumor micro-environmental cells and factors. This can explain why existing diffuse glioma therapies fail and why these tumors have remained incurable. Thus, there is a great need for innovation. We describe a novel strategy for the development of a more effective treatment of diffuse glioma. Our approach centers on gaining control over the behavior of the microglia, the defense cells of the CNS, which are manipulated by malignant glioma and support its growth. Armoring microglia against the influences from glioma is one of our research goals. We further discuss how microglia precursors may be genetically enhanced to track down infiltrating glioma cells.

A novel lncRNA‐LINC01116 regulates tumorigenesis of glioma by targeting VEGFA

“…Brain glioma is the most common primary tumor of the central nervous system, and one of the main causes of death in patients with intracranial tumors . The poor prognosis and high recurrence rate of glioma is largely due to the abundant blood flow, rapid growth, susceptibility of invasion to surrounding normal brain tissues and resistance to radiotherapy and chemotherapy .…”

“…Brain glioma is the most common primary tumor of the central nervous system, and one of the main causes of death in patients with intracranial tumors. [1][2][3][4] The poor prognosis and high recurrence rate of glioma is largely due to the abundant blood flow, rapid growth, susceptibility of invasion to surrounding normal brain tissues and resistance to radiotherapy and chemotherapy. [5][6][7][8] The tumorigenesis of glioma is biologically complex, involving a series of pathophysiological changes, and expression changes of many genes and signaling pathways.…”

Engineering Controlled Peritumoral Inflammation to Constrain Brain Tumor Growth

“…Pathways related to cytotoxic and phagocytic functions of microglia require microglia to upregulate the expression of complement and Fc‐gamma receptors. Activation of phagocytes, including microglia, is the most common function of Fc receptors, indicating that Zpep was acting in part via microglial cells in vivo . In stark contrast, animals dosed with AuNP‐P showed enrichment of pathways related with neuronal cell communication and synaptic transmission, reminiscent of a quiescent microenvironment that allows for tumor growth.…”

Checkpoints to the Brain: Directing Myeloid Cell Migration to the Central Nervous System

“…This is possibly due to systemic immunosuppression caused by the glioblastoma itself [195]. In the future it may become possible to enhance dendritic cell function by altering genes involved in antigen presentation or response to systemic immunosuppression, or it may be necessary to target a different subset of cells for optimal response, such as tumour-associated macrophages/microglia [196]. Interestingly, transplantation of gene-modified hematopoietic stem cells (the precursors to infiltrating macrophages) has also been tested in humans, but only for the purpose of mediating the myeloablative side-effects of high dose chemotherapy [197,198].…”