Skull-eating brain cancer stuns scientists

“Our discovery that this difficult-to-treat brain cancer interacts with the body’s immune system may help explain why current treatments—all of which treat glioblastoma as a localized disease—fail, and will hopefully lead to better therapeutic strategies for neurosurgery,” said the department’s microsurgical author. Einstein, a member of the National Cancer Institute (NCI)-MECCC.

According to the NCI, approximately 15,000 people are diagnosed with glioblastoma each year. The average survival for those who receive standard treatment of surgery, chemotherapy and radiation is about 15 months.

The marrow issue

As is the case with other bones, the skull contains marrow in which immune cells and other blood cells are formed. Dr. Brennan’s research into glioblastoma and the skull has been prompted by recent studies revealing extremely thin channels that connect the skull to its underlying brain, allowing molecules and cells to travel between the cranial marrow and the brain.

Dr. Brennan and his colleagues used advanced imaging techniques on mice that developed two different types of gliomas. They found that the tumors eroded the skull bones, especially along the sutures where the skull bones fuse. Such erosions appear to be unique in glioblastoma and other intracranial malignancies, because they do not occur with strokes, other types of brain damage, or even other systemic cancers. Computed tomography (CT) images of patients with glioblastoma revealed that the decrease in skull thickness is present in the same anatomical regions as in mice.

Skull erosion in mice has been found to increase the number and diameter of the cranial canals to the bone. The researchers hypothesized that these channels might allow glioblastomas to transmit signals to the cranial marrow that could profoundly alter the immune landscape.

A tendency toward inflammation

Using single-cell RNA sequencing, the researchers found that glioblastomas dramatically shifted the balance of myeloid immune cells in favor of pro-inflammatory myeloid cells—almost doubling levels of inflammatory neutrophils, while eliminating several types of antibody-producing B cells as well as other B cells.

“The cranial-to-brain conduits allow the influx of these numerous pro-inflammatory cells from the cranial marrow into the tumor, making the glioblastoma increasingly aggressive, often irreversible,” said study co-author, author, author, author, author, author, author, author, author, author, author, author, author, author, author, author, author, author, author, author, author, author, author, author. “Treat it.” “This indicates a need for treatments that restore the normal balance of immune cells in the cranial marrow of people with glioblastoma. One strategy would be to suppress the production of pro-inflammatory neutrophils and monocytes, while at the same time restoring T and B cell production.”

Interestingly, and adding to evidence that glioblastoma is a systemic rather than local disease, the skull and femur reacted differently to cancer. Glioblastomas activated several genes in the cranial marrow that enhanced the production of inflammatory immune cells; But in the femur marrow, the cancer-suppressed genes required the production of several types of immune cells.

The researchers wondered whether giving antispasmodic drugs that prevent bone loss would affect osteochondrosis, glioblastoma, or both. To find out, they gave mice with glioblastoma tumors two different drugs approved by the US Food and Drug Administration to treat osteoporosis. Both drugs (zoledronic acid and denosumab) stopped skull erosion — but one (zoledronic acid) also fueled tumor progression in one type of glioblastoma. Both drugs also blocked the beneficial effects of anti-PD-L1, an immunotherapy drug that boosts levels of tumor-fighting T cells.

the Nature Neuroscience The paper is titled “Brain Tumors That Extensively Induce Calvarial Osteogenesis and Alter the Immunological Landscape of the Cranial Marrow.” Additional MECCC and Einstein authors include Abhishek Dubey, Biljana Stangleland, Imane Abbas, David Fooksman, Ph.D. , Wade R. Koba, BS, Jinghang Zhang, MD, Benjamin T. Himes, Ph.D. Dobrenis, Ph.D. , Qinge Ye, Kevin Fisher, and Emad Eskandar, MD. Other authors include Erika Yamashita, Yutaka Uchida, and Masaru Ishii, at Osaka University, Osaka, Japan, Robert A., Olivia R. Lou winson s. He is at the University of California, San Francisco, California, and the Alexander Wehrler is at the German Rheumatology Research Center (DRFZ) and Freie Universität Berlin, Berlin, Germany.