Researchers in Germany report they have found islands of highly potent immune cells in the bone marrow of the skull neighboring glioblastoma, a surprising discovery that provides a prospective new avenue for the development of therapies to fight the most common form of brain cancer.
Until now, the common notion of the immune system has been holistic. That is, it operates as a single system that deploys immune cells to different parts of the body that are in need of defense against disease, infections, and the like. “What we have found is surprising and fundamentally new,” said Björn Scheffler, a researcher with the German Cancer Consortium (DKTK) at the West German Tumor Center Essen. “Our data show that highly potent immune cells gather in regional bone marrow niches close to the tumor and organize the defense from there. At least this is the case with glioblastomas.”
The research, published in Nature Medicine, build on findings from earlier animal experiments. To confirm what they had discovered, researchers collected tissue samples from the bone marrow near the tumor in the skull of patients who had not been treated for glioblastoma. They discovered that bone marrow niches in proximity to the glioblastoma appeared to be the source of immune cells which mount the anti-tumor defense. The researchers also found their samples also contained mature T lymphocytes—CD8 cells that are known to be highly effective cancer fighting cells—in the bone marrow close to the tumor.
The investigators also determined that the CD8 cells in the bone marrow had an increased number of receptors on the surface to control mature T lymphocyte proliferation. Further, descendants of these cell clones were found in both the bone marrow and in the adjacent tumor tissue, proving that the immune cells in the marrow were attacking the brain tumor. “We were able to show that the course of the disease correlates with the activity of the local CD8 cells,” Scheffler added.
While their findings will cause the field to adjust its concept of how the immune system works, it also provides a cautionary tale that current methods of treating glioblastoma may interfere with the immune system’s defense against these types of tumors. The investigators noted that surgery to open the skull for tumor resection may actually destroy a vital population of immune cells fighting the disease.
“In view of the new findings, we find ourselves in a dilemma: we have to gain access to the tumor in order to remove it and also to be able to confirm the diagnosis. There is currently no other way than through the skull,” said Ulrich Sure, director of the department of neurosurgery and member of the Essen research team. “But we are thinking about how we can minimize damage to the local bone marrow in the future.”
Minimizing this damage to the local bone marrow could be vital to developing new strategies to effectively treat glioblastoma, since this research showed that the proximal cranial bone marrow “may be the primary target for tumor-reactive T cell recirculation and T cell memory formation in humans,” the researchers noted.
While checkpoint inhibitor therapies have not been effective as a treatment modality for glioblastoma, finding ways to tap into this naturally occurring immune engine near the tumor could suggest new therapies related to local engaging of T cells, cellular therapies, or tumor vaccination, the team noted.
“We now know that highly potent immune cells are indeed present on site. We were able to prove that they are fit to fight tumors, but they are not capable of destroying the tumor on their own,” Scheffler concluded. “This is where we can start. One challenge will be to deliver drugs in sufficient concentration to the regional bone marrow niches at the right time. If we succeed, we may have a chance of controlling the growth of glioblastomas and improving our patients’ chances of survival.”
