Immunomodulatory Effect of Microglia-Released Cytokines in Gliomas

Abstract

Microglia, a type of differentiated tissue macrophage, are considered to be the most plastic cell population of the central nervous system (CNS). Microglia substantially contribute to the growth and invasion of tumor mass in brain tumors including glioblastoma (GB). In response to pathological conditions, resting microglia undergo a stereotypic activation process and become capable of phagocytosis, antigen presentation, and lymphocyte activation. Considering their immune effector function, it is not surprising to see microglia accumulation in almost every CNS disease process, including malignant brain tumors. Large numbers of glioma associated microglia and macrophages (GAMs) can accumulate within the tumor where they appear to have an important role in prognosis. GAMs constitute the largest portion of tumor infiltrating cells, contributing up to 30% of the entire glioma mass and upon interaction with neoplastic cells. GAMs acquire a unique phenotype of activation, including both M1 and M2 specific markers. It has been demonstrated that microglia possess a dual role: on one hand, microglia may represent a CNS anti-tumor response, which is inactivated by local secretion of immunosuppressive factors by glioma cells. On the other hand, taking into account that microglia are capable of secreting a variety of immunomodulatory cytokines, it is possible that they are attracted by gliomas to promote tumor growth. A better understanding of microglia-glioma interaction will be helpful in designing novel immune-based therapies against these fatal tumors. Concluding, as microglia significantly may contribute to glioma biology, favoring tumor growth and invasiveness, these cells represent a valuable alternative/additional target for the development of more effective treatments for gliomas.

Fas/FasL Contributes to HSV-1 Brain Infection and Neuroinflammation

“…In HSV-1 infected lpr and gld mice we found high levels of infiltrating monocytes in the CNS, suggesting that these cells can be cleared via a Fas/FasL-dependent pathway. We found no difference in the numbers of microglia in Fas/FasL-deficient animals which is in line with the fact that microglia are resistant to Fas/FasL-mediated apoptosis ( 41 , 55 ).…”

COVID-19-Induced Stroke and the Potential of Using Mesenchymal Stem Cells-Derived Extracellular Vesicles in the Regulation of Neuroinflammation

“…Microglia activation is the hallmark of neuroinflammation and occurs immediately following stroke (He et al 2020 ). The M1 polarized microglia are functionally characterized by the capability of eliminating microorganisms or tumor cells (Lanza et al 2021 ). They also release proinflammatory cytokines (IL-1 β , IL-6, IL-12, IFN- γ , and TNF), chemokines (CCL-2, CCL-20), CXCL-10, and cytotoxic substances, including reactive oxygen species (ROS), reactive nitrogen species, excitatory amino acids, and prostaglandins E2 (Liu et al 2019 ).…”

“…These proinflammatory factors, particularly inducible nitric oxide synthase, have cytotoxic effects on neurons, leading to neuronal loss, disruption of the blood–brain barrier (BBB) and the degradation of the extracellular matrix (ECM) (Zhang et al 2021a , b ). Alternatively, M2 microglia induces phagocytosis of dead neurons stronger and is associated with neural survival, reduction of brain damage, and restriction of destructive immune response (Lanza et al 2021 ; Zhang et al 2021a , b ). M2 phenotype is activated to exert a beneficial role following IS by producing anti-inflammatory and neuroprotective mediators including, IL-10, IL-4, and TGF- β (Jiang et al 2020 ).…”

The Use of Iron Oxide Nanoparticles to Reprogram Macrophage Responses and the Immunological Tumor Microenvironment

“…IONPs have also been used to track microglia and assayed as a potential nanocarrier in brain tumors. Microglia are highly phagocytic cells found entirely in the central nervous system (CNS) where they protect the nervous tissue from debris and damaged CNS structures and from viruses, microorganisms, and tumors (123)(124)(125)(126). Therefore, like macrophages, microglia can phagocytose IONPs and react to them.…”