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Updated: Jun 5, 2026
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
S100B attenuates microglia activation in gliomas: possible role of STAT3 pathway
Leying Zhang1, Wei Liu, Darya Alizadeh
1Division of Neurosurgery, Department of Surgery, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA.
Abstract:
Despite significant infiltration into tumors, the effector function of macrophages (MPs) and microglia (MG) appears to be suppressed in gliomas. Although STAT3 pathway is thought to play a role in this process, the exact mechanism by which gliomas induce STAT3 activation in MPs and MG is not known. Because activation of receptor for advanced glycation end products (RAGE) can induce STAT3, and because gliomas express high levels of S100B, a RAGE ligand, we hypothesized that MP/MG STAT3 activity may be modulated through S100B-RAGE interaction. Exposure of N9 MG and bone marrow-derived monocytes (BMM) to GL261 glioma condition medium (GCM) and low (nM) levels of S100B increased RAGE expression, induced STAT3 and suppressed MG function in vitro. Furthermore, neutralization of S100B in GCM, partially reversed IL-1β suppression in BMM, suggesting that the inhibitory effect of GCM to be in part due to S100B. Finally, blockage of S100B-RAGE interaction inhibited STAT3 activation in N9 MG and in glioma MG/MP in vivo. These findings suggest that the RAGE pathway may play an important role in STAT3 induction in glioma-associated MG/MPs, and that this process may be mediated through S100B.
Insights
Glioma suppresses immune cells like macrophages and microglia by activating the STAT3 pathway. The S100B protein interacts with RAGE, driving this STAT3 activation and immune suppression in brain tumors.
Area of Science:
- Neuro-oncology
- Immunology
- Cellular Signaling
Background:
- Macrophages (MPs) and microglia (MG) are immune cells that infiltrate gliomas but exhibit suppressed effector function.
- The STAT3 signaling pathway is implicated in this immune suppression, but the precise mechanism of its activation by gliomas remains unclear.
- Gliomas express S100B, a ligand for the Receptor for Advanced Glycation End Products (RAGE), which is known to activate STAT3.
Purpose of the Study:
- To investigate the hypothesis that the S100B-RAGE interaction modulates STAT3 activity in glioma-associated MPs and MG.
- To elucidate the role of the S100B-RAGE axis in STAT3 induction and subsequent immune suppression within the glioma microenvironment.
Main Methods:
- In vitro exposure of microglia (N9) and bone marrow-derived monocytes (BMM) to glioma-conditioned medium (GCM) and S100B.
- Assessment of RAGE expression, STAT3 activation, and immune cell function.
- In vivo experiments involving blockage of the S100B-RAGE interaction in glioma models.
Main Results:
- Exposure to GCM and S100B increased RAGE expression, induced STAT3 signaling, and suppressed MG function in vitro.
- Neutralization of S100B partially reversed IL-1β suppression in BMM, indicating S100B's contribution to GCM's inhibitory effects.
- Blocking the S100B-RAGE interaction effectively inhibited STAT3 activation in both in vitro and in vivo glioma models.
Conclusions:
- The S100B-RAGE pathway plays a significant role in inducing STAT3 activation in glioma-associated microglia and macrophages.
- This interaction is a key mechanism by which gliomas suppress the anti-tumor immune response mediated by these myeloid cells.
- Targeting the S100B-RAGE interaction presents a potential therapeutic strategy for overcoming immune suppression in gliomas.
