Glioma, a deadly type of brain tumor with a dismal prognosis, is very hard to treat. Our immune system cannot easily reach the tumor site due to the barriers that surround the brain.
To treat brain cancer, killer immune cells such as T lymphocytes need to be activated and primed in our lymph nodes. However, several barriers around the brain make it challenging for T lymphocytes to reach the tumor.
In a new study, scientists at Uppsala University have discovered structures similar to lymph nodes where T lymphocytes could be activated. These lymph node-like structures were found near the tumor in brain cancer patients.
In addition, it was also discovered that immunotherapy enhanced the formation of these structures in a mouse model.
Alessandra Vaccaro, a Ph.D. student at the Department of Immunology, Genetics, and Pathology and shared the first author of the study, said, “It was fascinating to discover for the first time the presence of lymph node-like structures in glioma patients. These structures are known as tertiary lymphoid structures (TLS), and they are not found in healthy individuals. They have all the components needed to support lymphocyte activation on-site, which means that they could have a positive effect on the anti-tumor immune response.”
The study on the mice models demonstrated that systemic delivery of αCD40 in preclinical glioma models induces the formation of tertiary lymphoid structures (TLS) in the proximity of meningeal tissue. It also counterproductively inhibited the tumor-killing ability of the T lymphocytes.
Anna Dimberg, who has led the study, said, “Learning that immunotherapies can modulate the formation of tertiary lymphoid structures in the brain offers exciting opportunities to find new ways of regulating the anti-tumor immune response in glioma.”
- van Hooren, L., Vaccaro, A., Ramachandran, M. et al. Agonistic CD40 therapy induces tertiary lymphoid structures but impairs responses to checkpoint blockade in glioma. Nat Commun 12, 4127 (2021). DOI: 10.1038/s41467-021-24347-7