By creating a registry of tumor-infiltrating cells, researchers are hopeful that they can develop effective and personalized treatments for kids with brain cancer.
Immunotherapy, a class of treatments that harness the power of the body’s own immune system to fight disease, has been a game-changer in improving the prognosis of some pernicious cancers throughout the past two decades.
Thanks in part to immunotherapy, the five-year survival rate for acute lymphoblastic leukemia, the most common type in children, has increased to 90%.
Scientists have been studying the potential of immunotherapy for treating pediatric brain cancers, which have surpassed leukemia as the leading cause of cancer deaths in children.
Because children’s brains are still developing, conventional therapies like surgery, chemotherapy, and radiation, mainstays in treating adults, can be risky in children. Furthermore, many of these tumors arise in critical, often inoperable, regions of the brain, such as the brain stem.
Immunotherapy presents an alternative—but there is still more work to be done to make it more effective for a wider range of tumors.
“The issue with brain cancers in children [versus adults] is they are very diverse with many, many different tumor types, and each one of them needs to be treated differently,” says Itay Raphael, a PhD research assistant professor of neurological surgery at the University of Pittsburgh.
“A big challenge with immunotherapy is finding specific targets, or antigens, on the cancer cells that the immune system can recognize and attack without harming healthy cells. Kids’ brain tumors don’t always have a lot of these clear targets.”
Using 1,000 pediatric brain tumor samples collected through the Children’s Brain Tumor Network, a medical research consortium of 35 medical centers, Raphael and his colleagues at the School of Medicine and UPMC Children’s Hospital of Pittsburgh sought to understand how the children’s immune systems were interacting with these cancers.
The results of the study appear in Science Translational Medicine.
The scientists looked at the tumor-infiltrating lymphocytes (TILs), a subset of immune cells known as T cells, that had infiltrated the tumors. The presence of TILs within a tumor indicates that the immune system has recognized targets on cancer cells, called antigens, as foreign and has sent immune cells to attack them. The TILs then multiply, in a process called clonal expansion, to kill the cancer. The study was the first to look at the T cell “clonal repertoire” and expansion in this sample group.
Because of how varied brain tumors and their antigens are, understanding the tumor’s molecular composition can help clinicians personalize each patient’s treatment. In a type of adaptive immunotherapy called TIL therapy, these T cells could then be extracted, engineered, and amplified in the lab, and then reinfused into the patient to mount a more robust and targeted anti-tumor response.
The information gathered from analyzing the T cells was also used to classify brain tumors based on the body’s cancer-fighting immune response and, ultimately, to tailor cancer therapies to each patient’s unique immune response.
Traditionally, these cancers are categorized based on the characteristics of the tumor cells themselves, including their genetic mutations and appearance. This research suggests that analyzing the immune response within the tumor could provide additional crucial information, potentially helping doctors better predict how a patient will respond to immunotherapy and modify treatment strategies accordingly.
The researchers are now evaluating the feasibility of doing clinical trials to test the intervention, notes Raphael.
“We’re trying to make the safest drugs for the safest treatment for the patients,” says Gary Kohanbash, a PhD associate professor of neurological surgery and immunology at Pitt and a coauthor of the study.
“This represents a step forward in developing immunotherapies for these patients that are personalized. These are such complex tumors, and they’re so different between patients. This [new knowledge] takes us closer to being able to address pediatric brain tumors more thoughtfully, carefully, and better.”
Source: University of Pittsburgh
