Immune sensitivity links race and survival after prostate cancer immunotherapy

Black men with advanced prostate cancer have a greater chance of survival after immunotherapy treatment, at least in part, because of ancestral gene variants in immune responses.

That connection is described in a new study by researchers at Duke Cancer Institute and published recently in the journal Cancer Research Communications.

Black men are 70% more likely than white men to have prostate cancer and die at higher rates from the disease, according to the American Cancer Society.

For men with metastatic prostate cancer that has progressed despite hormonal therapy, sipuleucel-T (marketed as Provenge) is the only effective and FDA-approved immunotherapy. While this therapy extends life in all such patients, DCI researchers have recently found that Black men have the greatest survival benefit with this therapy. However, the reasons for this have been unclear until now.

“Our team aims to understand what drives response to immune-based cancer therapies,” said study co-lead author Smita Nair, Ph.D., a professor in the departments of Neurosurgery, Surgery, and Pathology.

The researchers built on previously reported findings identifying ancestral differences in how certain proteins called toll-like receptors sense pathogens and direct immune responses. This genetic link has been described in other inflammatory contexts, such as fighting infectious diseases caused by viruses or bacteria, but has not been previously linked to cancer or immunotherapy for cancer. The Duke team’s findings could help doctors identify patients who may benefit from sipuleucel-T immunotherapy, which uses a patient’s own cells to fight cancer.

“These findings suggest the importance of ancestry to immunotherapy responses in cancer and may suggest therapeutic mechanisms to improve the benefits of immunotherapy in all patients,” said Andrew Armstrong, M.D., a co-author and an oncologist specializing in prostate cancer at DCI.

“Understanding the factors that promote or limit our immunity to cancer may be critical to developing new combinations to enhance anticancer effects, or biomarkers to identify those most likely to benefit.”

Researchers tested blood samples from more than 100 men with prostate cancer across two independent trials involving sipuleucel-T therapy. They found that study participants with a strong response to the therapy were more likely to carry a genetic variant that encourages immune cells to spark an inflammatory response that helps the body fight cancer. The variant is more commonly found in Black men, but was observed in both white and Black men.

“Our findings link the sensitivity of a patient’s immune system with outcomes after immunotherapy in prostate cancer,” said co-lead author Michael Brown, Ph.D., assistant professor in Duke’s Department of Neurosurgery. “This sensitivity was greater in Black individuals, possibly explaining why Black men with prostate cancer live longer after immunotherapy.”