Black men diagnosed with advanced prostate cancer may experience improved survival rates following immunotherapy, partly due to inherited gene variants that influence immune responses.
This link is highlighted in a recent study conducted by researchers at the Duke Cancer Institute, which was published in the journal Cancer Research Communications.
According to the American Cancer Society, Black men are 70% more likely than their white counterparts to develop prostate cancer and have higher mortality rates related to the disease.
For individuals with advanced prostate cancer that has continued to grow despite hormonal treatment, sipuleucel-T (known commercially as Provenge) is the sole FDA-approved and effective form of immunotherapy. This treatment prolongs life for all patients, but recent findings from DCI researchers indicate that Black men gain the most significant survival advantage from it. The reasons behind this have remained uncertain until now.
“Our research team is interested in understanding the factors that influence responses to immunotherapies for cancer,” explained Smita Nair, Ph.D., one of the study’s co-lead authors and a professor in the departments of Neurosurgery, Surgery, and Pathology.
Building on earlier research, the scientists examined genetic variations that affect how certain proteins called toll-like receptors recognize pathogens and initiate immune responses. These genetic differences have been observed in other contexts related to inflammation, such as infections from viruses or bacteria, but their connection to cancer and cancer immunotherapy had not been previously established. The findings from the Duke research team may aid in identifying patients who could benefit from sipuleucel-T therapy, which employs a patient’s own immune cells to combat cancer.
“Our results highlight the significance of ancestry in the effectiveness of immunotherapy for cancer and could offer insights into treatment strategies that enhance immunotherapy benefits for all patients,” noted Andrew Armstrong, M.D., a co-author and prostate cancer specialist at DCI. “Understanding the elements that enhance or hinder our immune defenses against cancer might be vital for developing new combinations to boost anticancer effects, or for identifying biomarkers that predict which patients are most likely to respond well.”
The researchers analyzed blood samples from over 100 men with prostate cancer participating in two separate trials of sipuleucel-T therapy. They discovered that participants who showed a strong response to the treatment were more likely to have a genetic variant that activates immune cells, promoting an inflammatory response that aids in the fight against cancer. This variant is more prevalent among Black men, although it was also found in white men.
“Our research connects the responsiveness of a patient’s immune system with the effectiveness of immunotherapy in prostate cancer,” stated co-lead author Michael Brown, Ph.D., an assistant professor in Duke’s Department of Neurosurgery. “This immune responsiveness was notably higher in Black individuals, which may help explain the better survival rates observed in Black men with prostate cancer after immunotherapy.”
Alongside Brown, Nair, and Armstrong, the study’s authors include Vincent M. D’Anniballe, David Boczkowski, Harini Kandadi, Nadeem Sheikh, William Kornahrens Jr., Elisabeth I. Heath, Archana Thakur, Wei Chen, Lawrence Lum, Frank C. Cackowski, Julie Boerner, and Michael D. Gunn.
This study was supported by funding from the National Institutes of Health Cancer Center Support Grants (P30CA014236, P30CA22453) and Dendreon Pharmaceuticals, which produces sipuleucel-T.
