Treatment to increase white blood cells may benefit glioblastoma patients

A new study led by the Washington University School of Medicine in St. Louis reveals at least one cause for low white blood cell counts in patients treated for glioblastoma, suggesting potential therapeutic strategies to improve survival in mice. it was done. Shown is her MRI scan of a patient with this type of brain tumor.

Patients with glioblastoma, a devastating brain tumor, often undergo treatments that lead to the unfortunate side effect of low white blood cell counts lasting six months to a year. Low white blood cell counts are associated with shorter survival, but the specific reasons for long-term decline in white blood cell counts and their association with shorter survival have puzzled scientists.

A new study led by the Washington University School of Medicine in St. Louis reveals at least one cause for low white blood cell counts in patients treated for glioblastoma, suggesting potential therapeutic strategies to improve survival in mice. it was done.

The study is published in the journal Science Translational Medicine.

Patients with this cancer usually do not live longer than 18 months. Standard treatment is radiation and chemotherapy. Many people then have a marked decrease in lymphocytes (a type of white blood cell) in the bloodstream. The cause of these low lymphocyte counts is something of a mystery as the treatment does not target the bone marrow where these cells originate and not all patients experience the problem.

Patients with low lymphocyte counts have been found to be worse than average. In order to improve their outcomes and extend their lifespan, we needed to understand what was causing the low white blood cell levels and how they contributed to poor survival.”

Jiayi Huang, MD, co-lead author, associate professor of radiation oncology, and co-clinical director of the Brain Tumor Center at Barnes Jewish Hospital and Saitman Cancer Center at the University of Washington School of Medicine

Huang and his colleagues at Siteman led a study collecting and analyzing blood samples from glioblastoma patients. About half of the patients had a low white blood cell count after treatment.

Researchers found that so-called myeloid-derived suppressor cells (a type of cell known to suppress the immune system) were significantly elevated in cells with low white blood cell levels. In mouse studies, scientists established a causal link between the irradiation-induced increase in bone marrow-derived suppressor cells and leukocyte suppression induced by tumor irradiation.

“We wanted to see if inhibitors could be used to block these myeloid-derived suppressor cells in order to improve therapeutic response to radiation.” Oklahoma Health Science Center. “Ultimately, when we tested the two inhibitors separately with radiation, we found that they significantly improved survival in multiple mouse models of this cancer.”

The researchers, including lead author Subhajit Ghosh, Ph.D., a postdoctoral fellow who conducted the study, first at the University of Washington and now at the University of Oklahoma, in Thotala’s lab, found that, on average, glioblastomas exposed to radiation alone All mice with tumors were still alive on day 120 when the experiment was terminated, with 50% to 60% of mice receiving either inhibitor and radiation.

One inhibitor, called CB1158, belongs to a class of drugs called arginase 1 inhibitors and is being investigated in clinical trials for the treatment of solid tumors, including colorectal, lung and bladder cancer. The second drug is a phosphodiesterase-5 inhibitor called tadalafil, which is approved by the Food and Drug Administration to treat other conditions such as erectile dysfunction and pulmonary hypertension.

“Bone marrow-derived suppressor cells have a normal function in the body,” said Huang, who is developing a clinical trial for glioblastoma patients. “During pregnancy, the body makes these cells to suppress immune cells so they don’t attack the embryo or fetus. But glioblastoma takes this normal process and uses it for its own purposes. In addition, irradiation of a tumor causes the body to produce large numbers of cells, and the amount of these cells leads to low white blood cell counts in patients, sometimes lasting for many months. Research suggests that targeting these cells in combination with radiation could be an exciting new strategy for improving the treatment of glioblastoma.

To further confirm their findings, the researchers conducted a small clinical trial of tadalafil combined with standard radiation in patients with glioblastoma. Researchers say the results are encouraging, with some patients responding well to the investigational treatment. The study is currently under review in another scientific journal. The researchers are also working to develop new therapeutics that have even more potential than her two inhibitors that block bone marrow-derived suppressor cells.