Older patients with a solid tumor responded with similar clinical outcomes to younger patients treated with immune checkpoint inhibitors, the results of a study published in Nature Communications showed. However, older patients did have divergent immune phenotypes compared with younger patients, and these phenotypes persisted through treatment, suggesting the necessity for age-tailored immunotherapeutic strategies.
“Older patients do just as well, sometimes better than younger patients with immunotherapy treatments,” stated senior author Daniel Zabransky, MD, PhD, Assistant Professor of Oncology, Johns Hopkins University School of Medicine. “We found clues about important pathways mediating the immune system response to immunotherapies in younger vs older patients that may help us improve the next generation of therapies or allow us to use current therapies in all patients more effectively.”
Study Methods and Results
The study authors sought to determine whether age-related immune changes impact responses to immune checkpoint inhibitors. They analyzed multiplex cytokine assay and high-parameter mass cytometry from blood samples of 104 patients with cancer who were receiving immune checkpoint inhibitors. Patients aged 65 or older (n = 54) showed similar clinical outcomes to younger patients (n = 50). Differences were seen, however, in the phenotype of immune cells in older patients of diminished cytokine responses, reduced pools of naive T cells with increased relative expression of immune checkpoint molecules, and more robust effector T-cell expansion in responders compared with nonresponders.
“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,” Dr. Zabransky 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.”
The study authors hope this research can help to develop new cancer therapeutics that are better tailored to different age groups without adding toxicities.
Disclosure: For full disclosures of the study authors, visit nature.com.
