The immunosuppressive microenvironment and immunotherapy in human glioblastoma

Abstract

Glioblastoma multiforme (GBM) is the most malignant intracranial tumor in adults, characterized by extensive infiltrative growth, high vascularization, and resistance to multiple therapeutic approaches. Among the many factors affecting the therapeutic effect, the immunosuppressive GBM microenvironment that is created by cells and associated molecules via complex mechanisms plays a particularly important role in facilitating evasion of the tumor from the immune response. Accumulating evidence is also revealing a close association of the gut microbiota with the challenges in the treatment of GBM. The gut microbiota establishes a connection with the central nervous system through bidirectional signals of the gut–brain axis, thus affecting the occurrence and development of GBM. In this review, we discuss the key immunosuppressive components in the tumor microenvironment, along with the regulatory mechanism of the gut microbiota involved in immunity and metabolism in the GBM microenvironment. Lastly, we concentrate on the immunotherapeutic strategies currently under investigation, which hold promise to overcome the hurdles of the immunosuppressive tumor microenvironment and improve the therapeutic outcome for patients with GBM.

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 ].…”

“…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 ].…”

Nanotechnology Meets Stem Cell Therapy for Treating Glioblastomas: A Review

“…Immunomodulatory approaches aim to harness the immune system against tumors and have by far revolutionized current cancer therapy by establishing therapeutic regimens in solid tumors . However, translating these approaches clinically has faced stumbling blocks in treating GBM as primary brain tumors exhibit a distinct and unique tumor microenvironment resulting in poor patient survival. , Although, some patients have seemed to benefit from immune checkpoint blockade (ICB), a major obstacle that limits the progress of ICB is the dynamic crosstalk between GBM cells and the immunosuppressive GBM microenvironment. − GSCs are mostly found in close proximity to myeloid-derived suppressor cells (MDSCs), where they engage and activate MDSCs to steer immune suppression . In addition to this, M2 macrophage polarization has been known to suppress antitumor responses regulated by the immune cell .…”

Editorial: Complexity of tumor microenvironment: A major culprit in cancer development, volume II

“…Various factors have been associated with cancer development and progression including recent research highlights concerning the metabolic ( 11 – 13 ) and other molecular factors ( 14 – 16 ). Notably, it has been well-established that metabolism and infiltrating cells in the TME represent attractive prognostic markers across a range of cancer types ( 17 , 18 ).…”