Sara Bjursten: Early detection of brain inflammation in immunotherapy

SARA BJURSTEN
Doctoral Thesis: Checkpoint inhibitor-induced adverse events in the CNS - T-cell characteristics and biomarkers
Research Area: Oncology
Sahlgrenska Academy, The Institute of Clinical Sciences

Where do you work and what is the basis of your research?
”I am an oncology specialist at Sahlgrenska University Hospital. My focus is on patients with metastatic melanoma, a highly lethal form of cancer. Most of these patients undergo immunotherapy, a recently developed treatment that stimulates the body’s T cells to attack tumor cells,” says Sara Bjursten. ”This therapy demonstrates remarkable effectiveness in roughly half of the cases, sometimes even leading to complete remission. However, an underlying risk is that the activated T cells can target healthy organs. These unpredictable immune responses can affect any organ.”

Potential paralysis and fatality

What is the main focus of your research?
”One of the most severe autoimmune responses is inflammation of the brain. If left untreated, this condition can lead to paralysis and, in the worst-case scenario, death. Detecting it early is crucial, but diagnosing brain inflammation is a challenge because the symptoms can easily be misinterpreted as infections or tumor progression. My research aims to identify blood markers that can facilitate the early discovery of this side effect. Another aim is to map out the activation of T cells, with the goal of developing more specific treatments for severe autoimmune reactions like brain inflammation.”

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A discovery that transformed approach

What are the most significant findings from your research, and how can they benefit patients?
”We have demonstrated that blood samples containing specific brain damage markers can significantly aid in diagnosing immunotherapy-induced brain inflammation at an early stage. This discovery has already led to changes in our practices. Blood tests have assisted us in diagnosing several cases of brain inflammation during the initial phases, allowing us to temporarily halt immunotherapy and swiftly initiate immune-dampening treatments. Additionally, we’ve found that patients with immunotherapy-triggered brain inflammation have a higher percentage of T cells expressing the stimulatory receptor (ICOS) compared to patients without such inflammation.”

Why did you choose to concentrate your studies on this particular immunotherapy side effect?
”In fact, it was a case in my clinical work that triggered the research. We had a patient who faced paralysis and was on the brink of death due to this side effect. The case was intense, and diagnosis proved to be a challenge. Initially, we assumed it might be a severe infection or rapid tumor growth. Struck by the scarcity of published material on immunotherapy-induced brain inflammation, we conducted an in-depth analysis of the patient’s journey, from the acute phase of the illness to recovery. Insights drawn from this single patient provided crucial breadcrumbs for our ongoing studies.”

Bridging science and patient impact

What has been particularly rewarding and enjoyable in your doctoral project?
”That my research is closely connected to my clinical work and my patients’ experiences has been incredibly rewarding. Given that immunotherapy is a relatively new treatment, clinicians often confront knowledge gaps regarding its side effects and optimal management. Through my research, I have explored some of these questions extensively. The knowledge garnered from these deep dives has been directly applicable to patients. For instance, the ability to detect brain inflammation earlier through a simple blood test,” Sara Bjursten says, adding:

”What also makes the research rewarding is the close collaboration between colleagues in the clinical and research settings. We are a small team catering to patients across the region, and our robust teamwork is rooted in recognizing the significance of advancing research.”

Text: Jakob Lundberg