Glioblastomas are aggressive brain tumors that are often difficult to treat, with patients typically having a life expectancy of less than two years if conventional therapies fail. Recently, a team of researchers from the German Cancer Consortium (DKTK) at the West German Tumor Center in Essen made an unexpected finding: they discovered clusters of powerful immune cells in the bone marrow of the skull, situated near glioblastomas, which play a crucial role in combating cancer. This new insight could pave the way for groundbreaking therapies, while also challenging existing treatment methods.
Immune system present
The Essen team relied on new data from animal studies and proceeded to take bone marrow samples from untreated glioblastoma patients in proximity to the tumor. First author Celia Dobersalske points out that, “it was essential to establish the methods for this procedure,” emphasizing that groundbreaking results stem from human tissue samples.
The researchers made a significant discovery: the bone marrow niches located near glioblastomas seem to serve as a source for mobilizing anti-tumor immune defenses. They identified not only active lymphoid stem cells, which can develop into immune cells, but also found mature cytotoxic T lymphocytes (CD8 cells) in the tumor-adjacent bone marrow. According to Dobersalske, “These immune cells are crucial for defending against cancer,” as they can identify and eliminate malignant cells.
The CD8 cells situated near the tumor displayed an increased number of receptors on their surfaces that regulate the proliferation of mature T lymphocytes. Additionally, similar cell clones—originating from the same cell—were found both in the bone marrow and the tumor tissue. This provides strong evidence that the immune cells present locally are actively combating the glioblastoma. “And they are successful—at least for a time,” notes Björn Scheffler. “We were able to show that the disease progression relates to the activity of the local CD8 cells.”
Are valuable immune cells being harmed?
This discovery not only overturns traditional views of immune system functionality but also necessitates a reevaluation of treatment strategies for glioblastoma. “Previously, we hadn’t considered the skullcap in our approaches. How could we have, given the lack of evidence suggesting the presence of potent immune cells there?” remarks lead author Scheffler.
“When we accessed the skull, we may have inadvertently harmed vital immune cells,” confirms Ulrich Sure, Director of the Department of Neurosurgery and part of the Essen research team. “Due to these new findings, we’re facing a dilemma: we need to reach the tumor for removal and to confirm the diagnosis. Currently, the only method involves going through the skull. However, we are brainstorming ways to reduce the impact on local bone marrow in future procedures.”
Conversely, the presence of local immune defenses creates exciting possibilities for new therapies. Specifically, checkpoint inhibitors, which are immunotherapeutic drugs designed to enhance the body’s cancer-fighting capabilities, are being reconsidered. However, these inhibitors have previously shown minimal success against glioblastomas.
“Numerous explanations have been proposed for this limited effectiveness, but we may need to reevaluate our understanding in this context,” Scheffler adds. “We now realize that potent immune cells exist locally. Our evidence indicates they are capable of attacking tumors, but they cannot eradicate the tumor independently. This presents an area for further exploration. A key challenge will be administering drugs in adequate concentrations to the regional bone marrow niches at the optimal time. If we can achieve this, we might significantly influence glioblastoma growth and improve survival rates for our patients.”
This research was supported by the Wilhelm Sander Foundation and the DKTK Joint Funding Program ‘HematoTrac’.
