Response to immune checkpoint inhibitors is as good in older cancer patients as in younger patients, despite age-related immune system differences, according to a study by researchers from the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy.
The new study was published in Nature Communications, and the lead author is Chester Kao, PhD, a postdoctoral fellow of the Department of Oncology, Johns Hopkins University School of Medicine. The study identifies some key differences in the immune response to these drugs in older patients compared with younger ones that may one day help clinicians further personalize therapies and boost treatment success.
People aged 65 or older are at the highest risk of cancer. These patients also have worse cancer treatment outcomes than their younger peers. The reasons for this are not entirely clear. Age-related changes that make the immune system less effective could make it harder for patients’ immune systems to fight cancer cells. Newer immune system-boosting therapies may help, but questions remain about whether age-related immune changes might blunt the drugs’ effects.
“Older patients do just as well, sometimes better than younger patients with immunotherapy treatments,” said senior author Daniel Zabransky, MD, PhD, an assistant professor of oncology at the Johns Hopkins University School of Medicine. “We found clues about important pathways mediating the immune system response to immunotherapies in younger versus older patients that may help us improve the next generation of therapies or allow us to use current therapies in all patients more effectively.”
The study examined immune cells and the cytokines they release in the blood of about 100 patients treated with immune checkpoint inhibitors for cancer. About half of the patients were aged 65 or older. Notably, both groups benefited from therapy equally, but there were differences in their immune responses and immune cells.
For example, certain T cells in older patients looked like “they’d been around the block,” Zabransky said, suggesting that they may be less ready to respond to threats such as cancer without additional treatments such as immune checkpoint inhibitors, making these drugs even more beneficial for older patients.
Next, Zabransky and his team want to look at differences in immune cells found inside tumors and compare them across age groups to see how they react to immunotherapies. They hope that by understanding age-related differences in immune responses to cancer therapies, they can either develop new cancer therapies better tailored to different age groups’ needs or find new ways to combine existing treatments to improve care. It’s imperative, he noted, to find ways to boost therapy effectiveness in older patients without triggering toxicities or other adverse events that can lead to poor outcomes.
“Right now, we give immune checkpoint inhibitors to patients in the same way without major consideration about how their age may influence how the immune system may recognize cancer cells,” he said. “By better understanding age-related changes that we all experience over our lifespan, we hope to identify new strategies and personalize our therapies even further based on those important patient-level factors.”
