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Updated: Feb 2, 2026
Microfluidic Co-Culture Models for Dissecting the Immune Response in in vitro Tumor Microenvironments
Published on: April 30, 2021
Upregulation of tumor suppressor WWOX promotes immune response in glioma
Zhao Yang1, Tianzhi Zhao, Yong Liu
1Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Abstract:
Previous studies demonstrate that human glioma cells could evade the host's immune surveillance system, result in aggressive proliferation. WWOX, a tumor suppressor gene affected in multiple cancers, induces tumor apoptosis and suppresses growth in vitro and in vivo. However, the effect of WWOX expression in glioma cells to immune cells is still unknown. In the present study, we transduced WWOX into human glioma cell line U251, and cocultured with Jurkat T cells together. We demonstrated that upregulation of WWOX could increase proliferation of Jurkat T cells and decrease the FasL and TGF-β expression of U251 cells, result in inhibiting apoptosis of Jurkat T cells. Therefore, our results suggested that loss of WWOX expression not only resulted in glioma carcinogenesis, but also suppressed immune cell attack by inducing Fas/FasL mediated apoptotic signaling.
Insights
Loss of WWOX expression in glioma cells promotes cancer and suppresses immune attack. Upregulating WWOX enhances T cell proliferation and inhibits glioma-induced apoptosis, suggesting WWOX is crucial for anti-tumor immunity.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Human glioma cells evade immune surveillance, leading to aggressive proliferation.
- The WWOX tumor suppressor gene induces apoptosis and suppresses tumor growth but its role in glioma-immune cell interactions is unknown.
Purpose of the Study:
- To investigate the effect of WWOX expression in glioma cells on immune cells.
- To elucidate the mechanisms by which WWOX influences the glioma-immune cell crosstalk.
Main Methods:
- Transduction of WWOX into the human glioma cell line U251.
- Co-culture of U251 cells with Jurkat T cells.
- Analysis of Jurkat T cell proliferation and apoptosis.
- Measurement of FasL and TGF-β expression in U251 cells.
Main Results:
- Upregulation of WWOX in U251 cells increased Jurkat T cell proliferation.
- WWOX upregulation decreased FasL and TGF-β expression in U251 cells.
- This resulted in the inhibition of Jurkat T cell apoptosis.
Conclusions:
- Loss of WWOX expression contributes to glioma carcinogenesis.
- Loss of WWOX suppresses immune cell attack by promoting Fas/FasL-mediated apoptosis signaling.
- WWOX plays a critical role in modulating the anti-tumor immune response in glioma.
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