Immunology and the Brain: Possible Cancer Treatments
Written by Pallavi Venkatesh
Edited by Elyse Ehlert
April 5, 2024
Edited by Elyse Ehlert
April 5, 2024
Research
The brain is responsible for running all the processes of the human body, an organized chaos of hundreds of moving parts in need of direction. Each part has an extremely specific function that fits into a large mechanism of interacting parts, with the brain at the head, running the show. For a long time, researchers believed that the brain had something called immune privilege, in other words, no immune presence. This theory is supported by the fact that the brain does not have a large number of lymphocytes, the body’s first defenders. The brain does not have T-cells, a type of lymphocyte that targets cancerous cells, active at all times. However, recent research has shown, the brain has a separate mechanism for immune responses. Microglia, an immune cell found in the brain, surveys the brain for injury or infection, and activates a T-cell response. Regardless, even with the presence of a functioning immune system, brain tumors flourish by many mechanisms, aptly avoiding immune responses. This is the idea explored in the article, Brain Immunology and Immunotherapy in Brain Tumors.
Glioblastoma, the most common malignant primary brain tumor in adults, is a leading cause of mortality. These tumors pose many complications. For one, the tumors have high intra-tumor heterogeneity. This means that the tumors have many varying and distinct populations within the same tumor, making it extremely difficult to target the cancerous cells, which can lead to the selection of resistant tumors. This phenomenon is called immunoediting: the immune system targets all the cells that release proteins that induce immune responses, or immunogenic antigens. The remaining cancerous cells are resistant to treatment. In addition, the cancerous cells in glioblastoma have a low mutational burden, meaning that it does not mutate as rapidly, making it difficult for the body to recognize. Due to both of these factors, immune checkpoint inhibitors are not successful in glioblastoma, despite being effective in other solid tumors.
So what is the standard recommended treatment? Scientists recommend a multimodal therapy, combining many treatments including surgery, radiation, and temozolomide (TMZ) chemotherapy. TMZ chemotherapy has an overall survival benefit to those newly diagnosed with glioblastoma, but it has limitations due to its toxicity. It often leads to immunosuppression, which in turn results in increased, possibly deadly, infections. To combat this, it is recommended that TMZ is coupled with lymphodeletion, the use of chemotherapy to kill T-cells, to help the body maintain a stable immune system. Another effective therapy that is recommended is using peptide and dendritic cell vaccines in tandem with other immunotherapies. These vaccines have been shown to be safe and increase overall immune responses. Overall, malignant tumors, particularly glioblastoma, are still extremely lethal diseases. While many strides are being made in immunotherapy, it does not significantly decrease the mortality of the disease. With further research, new immune therapies can be found that can successfully target the tumors, but for now, combination treatments are the best bet to beat glioblastoma.
References
Sampson, J. H., Gunn, M. D., Fecci, P. E., & Ashley, D. M. (2020). Brain immunology and immunotherapy in brain tumours. Nature Reviews Cancer, 20(1), 12-25.