Immune checkpoint inhibitors may work in brain cancers

New evidence that immune checkpoint inhibitors may work in glioblastoma and brain metastases was presented by Anna Sophie Berghoff, MD, at the European Society for Medical Oncology Symposium on Immuno-Oncology 2014 in Geneva, Switzerland.

The novel research shows that brain metastases have dense concentrations of tumor infiltrating lymphocytes, providing an immunoactive environment. Moreover, both primary and secondary brain cancers often exhibit high expression of the immunosuppressive factor known as programmed cell death ligand 1 (PDL1), which can be inhibited by new treatments, thus activating the immune system.

"Patients with glioblastoma and brain metastases have very few treatment options and usually die within a short period of time," said Berghoff, a resident at the Department of Medicine I, Comprehensive Cancer Centre-CNS Tumours Unit, Medical University of Vienna, Austria.

Immune checkpoint inhibitors are a new group of cancer treatments that work by boosting the patient's immune response to the tumor. The immune system operates differently in the brain in comparison to other organs.

"Our study was designed to find out whether the immune system is activated and working in brain tumors, which would provide the foundation for immune checkpoint inhibitors to work," Berghoff explained.

The study included 117 patients with glioblastoma and 116 patients with brain metastases. Using immunohistochemistry the researchers looked for the presence of T-cells, also called tumor infiltrating lymphocytes, in the tumors and whether they were accentuated in different areas of the tumor. T-cells are the main effector cells of the immune response and can be boosted by immune checkpoint inhibitors. They also looked for PDL1, which is an immunosuppressive protein that influences responses to immune checkpoint inhibitors.

The researchers found that patients with glioblastoma had fewer T-cells, and therefore less activation of the immune system, than patients with brain metastases who had high concentrations of T-cells. They also found that PDL1 was common in both glioblastoma and brain metastases, with glioblastoma showing particularly high PDL1 positivity.

"We saw that these brain tumor types have a different interaction with the immune system. The glioblastoma actively suppresses the immune system and there is little immune response. In contrast the brain metastases do a little less suppression of the immune system and there are a lot more tumor infiltrating lymphocytes," said Berghoff.

Berghoff said the findings demonstrate that the immune system interacts with glioblastoma and brain metastases, which is evidence that immune checkpoint inhibitors may work.

"We have arguments for conducting clinical studies with immune checkpoint inhibitors in patients with glioblastoma and brain metastases. In both tumor types we commonly see high expression of PDL1, an immunosuppressive factor which can be inhibited with new treatments. By inhibiting the suppression you can activate the immune system, which in theory, would work in brain cancers."

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