The Translational Immunology Program is studying the unique nature of the immune response in the brain to improve patient outcomes.
By Neuro-Oncology Branch Staff
June 28, 2022
Immunotherapy is an important area of research in neuro-oncology because of its potential to be an effective treatment for brain tumors. Research shows it can improve outcomes for many cancers, but for brain tumors more research is needed on the unique nature of the immune response in the brain and the characteristics of brain tumor patients that may contribute to treatment response.
That’s why Mark Gilbert, M.D., chief and senior investigator at NCI’s Center for Cancer Research, Neuro-Oncology Branch (NOB), is leading research in immunotherapy and precision medicine for brain tumors as head of the Translational Immunology Program.
“The research goals of the Translational Immunology Program are to create clinical studies that include a strong laboratory component to better understand why some patients respond to treatment and others do not,” says Dr. Gilbert. “We are also looking at the effects of other treatments on immune response and finding ways to either avoid these treatments or reverse their negative effects.”
Dr. Gilbert received his medical degree from Johns Hopkins University and completed residencies in internal medicine, neurology, and a neuro-oncology fellowship. Over the course of his 35-year career, Dr. Gilbert has been an integral part of various national and international clinical trial initiatives. His robust research program includes a multidisciplinary team of clinicians and scientists who aim to improve treatments and patient outcomes.
The Basics of Translational Immunology Research
Translational immunology studies ways to improve immunotherapy in clinical trials. Immunotherapy is a type of treatment that uses substances to stimulate or suppress the immune system to help the body fight cancer.
“When working properly, the immune system will recognize a virus or bacteria and then fight it. But when the immune system encounters abnormal cancer cells, without help, there is virtually no immune response,” says Dr. Gilbert. “This is because the cancer has developed a way to suppress an immune response by bringing in immune cells that are designed to suppress the immune function.”
Dr. Gilbert is studying ways to reduce the amount of immunosuppression that the body responds to, so that it is not fighting against efforts to generate an immune response. His research team uses a bench-to-bedside and back-to-bench approach. Meaning, findings from laboratory experiments are used to develop clinical trials. Then, clinical trial observations from the trial go back to the laboratory. This type of collaborative approach helps researchers and clinicians work together to improve outcomes for patients, and for other cancers, it has proved successful.
For example, a type of immunotherapy drug called immune checkpoint inhibitors have changed the cure rate for certain cancers from zero to over 40 percent. Unfortunately, the cure rate of glioblastoma, the most common type of brain tumor, is zero and the five-year survival rate ranges from five to 22 percent depending on the patient’s age. Dr. Gilbert and his team in the Translational Immunology Program are hopeful that their immunotherapy research will lead to similar advances in patients with brain tumors.
Their research is focused on developing combination therapies that can increase immune cells to the tumor site. Also, by understanding the characteristics of brain tumor patients, clinicians can improve patient selection on immunotherapy clinical trials to maximize treatment benefits for the patients.
A Discovery leads to a Clinical Trial
Almost every patient with a brain tumor is treated with steroids, but it was not well understood how steroids effect a patient’s response to immunotherapy. Dr. Gilbert’s lab did some of the early work investigating what happens to healthy immune cells in people without a brain tumor when treated with steroids. They discovered that steroids nearly completely prevent the immune cell’s ability to respond to immunotherapy.
“This was an important discovery because nearly every patient with a cancerous brain tumor is prescribed steroids. In some of the pivotal clinical trials, many patients were on steroids when they received immunotherapy,” says Dr. Gilbert. “Now that we know steroids prevent a response to immunotherapy, those patients, even if they could have responded, would not have responded because of the steroid medication.”
The discovery led to Dr. Gilbert and his team developing a clinical trial to monitor the immune system for people with glioblastomas who are not on steroids. The trial tests if immune checkpoint inhibitors given with standard treatment results in an immune response. “We are monitoring patient’s immune response in their blood to see if some have an immune response and have better outcomes, surviving longer than those who do not get an immune response,” shares Dr. Gilbert. This trial will also evaluate a test that may help determine who is likely to get that response.
Dr. Gilbert and his team are hopeful that this study may be the first to provide data that shows the possibility that an immune response could improve survival rates, suggesting that the immunotherapy is beneficial for people with glioblastomas.
Dr. Gilbert explains that if a patient gets an immune response in their blood, if these immune cells are able to move or traffic into the brain tumor, they will likely impact their brain cancer and improve outcomes. The next step is to figure out who gets the immune response by analyzing the clinical trial data. Researchers will evaluate the clinical characteristics like age, gender, and race, and genetic characteristics, comparing the responders and non-responders to the immunotherapy.
Determining what types of patients with glioblastomas have an immune response will help Dr. Gilbert and his team develop a clinical trial to study further the effects of immunotherapy.
The Future of Translational Immunology Research
Dr. Gilbert and his team collaborate with other NOB research programs that are conducting complementary immunology studies. They are also studying the immune microenvironment of tumor samples from a clinical trial that used a vaccine because a group of patients with glioblastoma on the trial had an unexpected long-term survival.
“This may give us insight into what the surrounding components of the tumor are in a setting where there is a good immune response,” says Dr. Gilbert. “Given the complexity of cancers in the central nervous system, we need to carefully understand what is unique in those cancers. So that when we use immunotherapy, we are doing whatever we can to enhance it, and not inadvertently disable it.”
Dr. Gilbert hopes to give immunotherapy every chance to be successful for patients with brain tumors. “Hopefully, we can emulate our colleagues in other cancers who have had some amazing successes with immunotherapy and provide our patients with the same improved outcomes.”