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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
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  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Oncology And Carcinogenesis
  9. Predictive And Prognostic Markers
  11. Targeting Wnt Signaling For Improved Glioma Immunotherapy.
  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Oncology And Carcinogenesis
  9. Predictive And Prognostic Markers
  11. Targeting Wnt Signaling For Improved Glioma Immunotherapy.

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Targeting Wnt signaling for improved glioma immunotherapy.

Margarita Gutova1, Jonathan C Hibbard2, Eric Ma2

  • 1Department of Stem Cell Biology and Regenerative Medicine, City of Hope Beckman Research Institute, Duarte, CA, United States.

Frontiers in Immunology
|March 7, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

This study shows that blocking Wnt/CBP/β-catenin signaling with ICG-001 can stop glioblastoma growth and enhance immune cell activity. This suggests ICG-001 may improve immunotherapy effectiveness for brain tumors.

Keywords:
ICG-001NanoString gene expressionWnt signaling, pathwaydifferentiation

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Area of Science:

  • Neuro-oncology
  • Cancer Immunology
  • Molecular Biology

Background:

  • Glioblastoma (GBM) is an aggressive brain cancer with poor prognosis despite standard treatments.
  • Wnt/β-catenin signaling activation in GBM correlates with poor outcomes and promotes glioma stem-like cell proliferation.
  • Current immunotherapies show limited efficacy in GBM due to tumor heterogeneity and antigen escape.

Purpose of the Study:

  • To investigate the effects of the Wnt/CBP/β-catenin antagonist ICG-001 on glioma cells and the tumor microenvironment (TME).
  • To assess ICG-001's impact on immune cell infiltration, vascularization, and metabolic changes in GBM.
  • To evaluate ICG-001's potential to enhance chimeric antigen receptor (CAR) T cell therapy for glioblastoma.

Main Methods:

  • Utilized patient-derived xenografts and murine glioma models (GL261, K-Luc).
glioma
immunotherapy
proteomics
  • Administered ICG-001 to assess its effects on glioma cell proliferation, differentiation, and gene expression (e.g., Survivin/BIRC5).
  • Analyzed immune cell infiltration (CD3+, CD8+), vascular markers (CD31), and gene expression in response to ICG-001, alone and in combination with CAR T cells.

    • Main Results:

    • ICG-001 demonstrated in vitro cytostatic effects and induced differentiation in glioma cells.
    • Treatment with ICG-001 downregulated the Wnt/CBP/β-catenin target gene Survivin/BIRC5.
    • ICG-001 enhanced CD3+ and CD8+ T cell infiltration and CD31 expression in a syngeneic glioma model.
    • Pre-treatment with ICG-001 followed by CAR T cell therapy showed improved immune cell infiltration compared to single treatments.

    Conclusions:

    • Specific Wnt/CBP/β-catenin antagonism with ICG-001 induces glioma stem cell differentiation and modulates the tumor microenvironment.
    • ICG-001 promotes immune cell activation and recruitment, suggesting a role in overcoming GBM resistance.
    • ICG-001 holds promise as an adjunct therapy to enhance the efficacy of immunotherapy in glioblastoma patients.