The overall research goal in our lab is to identify molecular mechanisms of immunosuppression and evasion in brain cancer and develop novel immunotherapeutic for these diseases. Glioblastoma is one of the most aggressive cancer with dismal 5-year survival rate less than 5% and remains incurable. The unique tumor microenvironment in the brain is extremely challenging for effective therapies. The current standard of care for GBM is a combination of surgery, chemotherapy and radiation, which are of limited efficacy and often cause devastating neurological side effects. Therefore, safer and more effective therapeutic modalities are needed for GBM.
Immunotherapies including immune checkpoint blockade or CAR-T therapy have transformed cancer treatment in multiple cancers but have not demonstrated clinical benefits in large scale clinical trial for brain cancer. Previously, we showed that the pharmacological inhibition of Protein Phosphatase 2A (PP2A) enhances the antitumor efficacy of anti-PD-1 antibodies in PD-1 blockade-resistant melanoma and colon cancer models. Building on this work, we found that PP2A inhibition sensitizes a mouse model of glioblastoma (GBM) to immune checkpoint therapy (ICT), and these findings have led to a phase II clinical trial testing PP2A inhibition as a single agent for recurrent GBM to assess the degree of drug penetration into brain tumor (NCT03027388).
In our lab, currently we focus on the following areas:
- Macrophage and Microglia mediated immunosuppression in glioblastoma.
- NK cell based therapy for pediatric brain cancer.
- Cancer intrinsic mechanisms that mediate immune evasion in brain cancer.