Researchers at Uppsala University have made a significant breakthrough in the treatment of aggressive brain tumors, particularly glioblastoma. In a study published in the journal Cancer Cell, they have developed a method to enhance the effectiveness of immunotherapy by enabling immune cells to penetrate the tumor.
Glioblastoma is a highly aggressive brain tumor that has proven difficult to treat due to its ability to evade the body’s immune response. While immunotherapy using checkpoint inhibitors has shown promise in reactivating the immune system against cancer, its effectiveness in brain tumors has been limited. The dysfunctional blood vessels in brain cancer act as a barrier, preventing killer T cells, an important component of immunotherapy, from reaching the tumor.
The Uppsala researchers tackled this challenge by utilizing a viral vector, AAV-LIGHT, which infected the brain’s blood vessels and triggered the production of a protein called LIGHT. This led to changes in the tumor blood vessels, enhancing their capacity to transport T cells from the bloodstream into the tumor tissue.
Their findings demonstrated that the viral vector altered the function and shape of the tumor blood vessels, enabling the recruitment of killer T cells into the tumor. Additionally, the therapy induced the formation of tertiary lymphoid structures (TLS), which resemble lymph nodes and have been associated with increased sensitivity to cancer immunotherapy. The presence of these structures, induced by AAV-LIGHT, created a favorable environment for killer T cell activity and resulted in prolonged survival and potential cures in experimental models.
Furthermore, the researchers observed that the therapy influenced the composition of the TLS, enriching them with T cells. This manipulation of TLS composition has the potential to be leveraged in various therapeutic settings. The treatment also promoted the presence of a specific subset of killer T cells called “stem-like T cells,” which exhibited enhanced therapeutic effects. These stem-like T cells were found within the TLS as well as in specialized niches formed around the tumor’s blood vessels.
While the viral vector, AAV-LIGHT, requires further development before clinical trials can begin, the results are highly promising. The researchers aim to advance this novel therapy and investigate its potential for treating patients with glioblastoma. If successful, this approach could significantly improve the prognosis and treatment options for individuals with this aggressive form of brain cancer.
Source: Swedish Research Council