Mayo Clinic Researchers Find a Way to Reprogram Immune Cells and Boost Chemotherapy Response in Glioblastoma

Mayo Clinic researchers have identified a potential new approach to treating glioblastoma that could help the immune system fight the aggressive brain cancer while improving the effectiveness of existing chemotherapy.

The preclinical research, published in Nature Communications, found that inhibiting the enzymatic activity of a protein called MALT1 can reprogram immune cells surrounding glioblastomas, shifting them from a state that helps protect the cancer to one that promotes an antitumor immune response.

Researchers also found that treatment with a MALT1 inhibitor slowed tumor growth in preclinical models and that combining MALT1 with temozolomide, the chemotherapy most commonly used to treat glioblastoma, enhanced temozolomide effectiveness. In one preclinical model, median survival substantially increased when this chemotherapy was combined with MALT1 inhibition in comparison to treatment with temozolomide alone.

"Glioblastoma is extraordinarily difficult to treat, in part because the tumor is able to manipulate the immune cells around it and create an environment that protects the cancer. Our findings point to a potential approach to disrupting that protection and, importantly, to making an existing treatment more effective," says Juliana (Hofstatter Azambuja) Yerneni, Ph.D., lead author and researcher in the Department of Laboratory Medicine and Pathology at Mayo Clinic.

Glioblastoma is the most common and aggressive primary cancerous brain tumor in adults and accounts for roughly 5% of malignant brain tumors in children. Despite surgery, radiation and chemotherapy, the cancer remains incurable and almost always returns.

The findings raise the possibility of a future approach that could help patients get more benefit from existing treatments.

"Our goals are to discover how glioblastoma communicates with the immune cells surrounding the tumor in order to dampen the antitumor immune response and to use these discoveries to identify new treatments that enhance antitumor immune response and improve outcomes for patients with this devastating disease," says Linda McAllister-Lucas, M.D., Ph.D., pediatric oncologist, enterprise deputy director for pediatric cancer programs of the Mayo Clinic Comprehensive Cancer Center and co-senior author of the study with Peter Lucas, M.D., Ph.D., vice chair for research in the Department of Laboratory Medicine and Pathology at Mayo Clinic.

More research is needed to determine which specific subtypes of glioblastoma may be most likely to respond to MALT1-targeted therapy and to evaluate its potential for use in patients.

Review the study for a complete list of authors, disclosures and funding.