The Glioma Immune Landscape: A Double-Edged Sword for Treatment Regimens

Abstract

Immune cells constitute a major part of the tumor microenvironment, thereby playing an important role in regulating tumor development. They interact with tumor cells, resulting in the suppression or promotion of glioma development. Therefore, in recent years, scientists have focused on immunotherapy that involves enhancing the immune response to fight the battle against cancer more effectively. While it has shown success against different cancer types, immunotherapy faces major roadblocks in glioma treatment. These involve the blood brain barrier, tumor heterogeneity and an immunosuppressive glioma microenvironment, among other factors. Additionally, the interaction of the peripheral immune system with the central nervous system provides another challenge for immunotherapeutic regimens. For modulating different immune cell populations to counter glioma cells, it is important to expand our knowledge about their role within the glioma microenvironment; therefore, herein, we review the different immune cell populations found in the glioma microenvironment and navigate through the various shortcomings of current immunotherapies for glioma. We conclude by providing an insight into ongoing pre-clinical and clinical trials for glioma therapies.

Identification and Validation of a PEX5-Dependent Signature for Prognostic Prediction in Glioma

“…Gliomas exhibit a distinct tumor microenvironment, largely due to the presence of the blood–brain barrier [ 26 ]. During glioma progression, the infiltrating macrophages, Tregs and MDSCs have been shown to have protumor and immunosuppressive effects [ 26 , 27 ]. To examine the potential role of these immune cells in the prognosis value of the PEX5-dependent model, we computed the abundance of the three types of immune cells in each glioma patient through ssGSEA [ 28 ].…”

“…Gliomas present a complex and unique immune microenvironment, largely due to the presence of the blood–brain barrier [ 26 ]. Within this microenvironment, various immune cell populations coexist, including macrophages, resident microglia, MDSCs, T cells, natural killer (NK) cells, and a small number of B cells [ 27 ]. Studies have shown that macrophages, Tregs, and MDSCs exert protumor and immunosuppressive effects during the progression of gliomas [ 26 , 27 ].…”

“…Within this microenvironment, various immune cell populations coexist, including macrophages, resident microglia, MDSCs, T cells, natural killer (NK) cells, and a small number of B cells [ 27 ]. Studies have shown that macrophages, Tregs, and MDSCs exert protumor and immunosuppressive effects during the progression of gliomas [ 26 , 27 ]. In gliomas, there is a noticeable shift in the polarization of tumor-associated macrophages (TAMs) from an M1 phenotype to an M2 phenotype, resulting in the suppression of the local immune response [ 50 , 51 ].…”

“…These findings offer insights into the potential mechanisms underlying the unfavorable prognosis associated with high-risk gliomas. Currently, immunotherapy has shown limited success in the treatment of glioma patients [ 27 ], and a major challenge lies in identifying the patients most likely to respond to this treatment. Therefore, our results provide valuable guidance for the development of personalized immunotherapy approaches for glioma patients.…”

From glioma gloom to immune bloom: unveiling novel immunotherapeutic paradigms-a review

“…Killer cell immunoglobulin-like receptors (KIRs) on NK cells play a critical role in NK cell function by interacting with MHC class I molecules on target cells. In glioma, increased KIR expression on NK cells and decreased ligand expression on tumor cells reduce NK cell activity [ 152 ]. However, studies indicate that activating KIR genes enhances NK cell efficacy against pediatric tumors [ 153 ].…”