Moffitt researchers discover immune-oncologic variations in prostate tumors of African American males
Prostate cancer is the most common cancer in American men after skin cancer, but the disease does not affect all races equally. African American men are almost twice as likely to develop prostate cancer and are more likely to have an aggressive form of the disease that grows and spreads rapidly. They are also twice as likely to die from prostate cancer than white men. While the health community is aware of this inequality, little is known about why prostate cancer affects African American men differently. It has become increasingly evident that both socio-economic and biological factors can contribute to inequality.
Researchers at the Moffitt Cancer Center are studying the genomic characteristics of prostate cancer tumors in men of various races to better understand why African Americans are more prone to the disease. In a new article published in Clinical Cancer Research, the research team describes the immuno-oncological differences in prostate cancer tumors in African American men and how these variations can be used to develop more personalized treatment approaches for this population.
Previous studies have looked at the immune landscape of prostate cancer in White or European-American men, but have not been validated in their African-American counterparts. Our genomic analysis, the largest of its kind, found that there are key immune pathways in African American men that are significantly elevated, which can correlate with the risk of cancer recurrence and poor outcomes. “
Kosj Yamoah, MD, Ph.D., lead study author and associate member of the Moffitt Radiation Oncology and Cancer Epidemiology Programs
Moffitt researchers analyzed entire transcriptome data from nearly 1,200 proctectomy specimens in the registry of the Decipher Genomic Resource Information Database. Transcriptomic data provides a complete overview of all RNA sequences within a cell, which in turn can show when and where each gene is switched on or off. The team focused on 1,260 immunospecific genes to determine differences between prostate cancer tumor cells in African-American and European-American men.
They discovered remarkable differences between the two races. Major immune pathways, including cytokine, interferon, and interleukin signaling, are elevated in African-American prostate tumors. These pathways can contribute to the growth and spread of cancer cells and escalate. The immunobiological signatures suggest that prostate cancer tumors in African American men may be more sensitive to radiation therapy and may respond better to immunotherapy.
“There are currently only two immunotherapy options for prostate cancer patients: the sipuleucel T-cell vaccine and pembrolizumab. However, not everyone responds to these therapies,” said Yamoah. “Our study shows that African American men have higher total immune levels in their tumor microenvironment and higher expression of T lymphocytes. We can use this information to select a therapy that better targets their tumor and therefore improves outcomes.”
The team also discovered six genes where expression levels were consistently different between African-American and European-American men. One gene, IFITM3, is often an indicator that a patient has a significantly higher risk of biochemical recurrence, meaning that their prostate antigen score continues to rise despite surgery or radiation. In addition to the progression of cancer, this gene also plays an important role in metastasis.
The researchers say more studies will be needed to determine whether their results may have beneficial effects on the treatment and management of prostate cancer in African American men.
H. Lee Moffitt Cancer Center & Research Institute
Awasthi, S. et al. (2020) Comparative genomics shows different immuno-oncological signaling pathways in African-American men with prostate cancer. Clinical cancer research. doi.org/10.1158/1078-0432.CCR-20-2925.