Moffitt researchers find immune-oncologic differences in prostate tumors of African American men



Prostate cancer is the most common type of cancer among American men after skin cancer, but the disease does not affect all races equally. African American men are nearly two times more likely to develop prostate cancer, and more often have an aggressive form of the disease that grows and spreads quickly. They are also two times more likely to die from prostate cancer compared to white men. While the health care community is aware of this disparity, little is known about why prostate cancer affects African American men differently. It has become increasingly evident that both socio-economic and biological factors may contribute to the disparity.

Moffitt Cancer Center researchers are taking a closer look at the genomic features of prostate cancer tumors among men of different races in hopes of better understanding why African Americans are more susceptible to the disease. In a new article published in Clinical Cancer Research, the research team describes the immune-oncologic differences in prostate cancer tumors of African American men and how those variations may be exploited 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 lacked validation among their African American counterparts. Our genomic analysis, the largest of its kind, revealed there are major immune pathways that are significantly elevated in African American men, which can correlate with risk of cancer recurrence and poor outcomes.”


Kosj Yamoah, M.D., Ph.D., lead study author and assistant member of the Radiation Oncology and Cancer Epidemiology Programs at Moffitt

The Moffitt researchers analyzed whole transcriptome data from nearly 1,200 proctectomy samples in the Decipher Genomic Resource Information Database registry. Transcriptomic data provides a complete look at all the RNA sequences within a cell, which in turn can show when and where each gene is turned on or off. The team focused on 1,260 immune specific genes to determine differences between prostate cancer tumor cells in African American and European American men.

They discovered striking 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 and escalate the growth and spread of cancer cells. The immune biologic signatures suggest prostate cancer tumors in African American men may be more sensitive to radiotherapy and could have a better response to immunotherapy.

“Currently there are only two immunotherapy options for prostate cancer patients: the sipuleucel-T cell vaccine and pembrolizumab. However, not everyone responds to those therapies,” said Yamoah. “Our study shows that African American men have higher overall immune content within their tumor microenvironment and higher expression of T lymphocytes. We can use that information to select a therapy that better targets their tumor and therefore improve their outcome.”

The team also discovered six genes that 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 their prostate antigen score continues to rise despite surgery or radiation. In addition to cancer progression, this gene also plays an important role in metastasis.

The researchers say further study will be needed to determine if their findings can have positive implications on the treatment and management of prostate cancer in African American men.

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Journal reference:

Awasthi, S., et al. (2020) Comparative genomics reveals distinct immune-oncologic pathways in African American men with prostate cancer. Clinical Cancer Research. doi.org/10.1158/1078-0432.CCR-20-2925.



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Using stem cells, researchers describe how developing neurons are blocked and tumors started — ScienceDaily


Atypical teratoid rhabdoid tumors (ATRT) are a rare, fast-growing form of brain cancer that usually strikes children three years and younger, though they can occur in older children and adults. There are multiple treatments, but no definitive standard of care and long-term survival is poor.

The cause of ATRT is primarily linked to inactivation of a gene called SMARCB1, part of a larger complex that helps regulate gene expression and developmental processes. In a study published online September 10, 2020 in the journal Genes & Development, an international team of scientists, led by researchers at University of California San Diego School of Medicine and the San Diego Branch of the Ludwig Institute for Cancer Research, describe how the loss of the gene negatively impacts neural development and promotes tumor growth.

“Previous research has established that, unlike some cancers, ATRT is predominantly associated with the functional loss of a single gene — SMARCB1 — which leads to tumor development through changes in how genes are expressed rather than the combined effect of multiple gene mutations,” said senior author Frank Furnari, PhD, professor of pathology and Ludwig San Diego member.

“ATRT is a very deadly cancer with very few effective therapies, which are complicated by the negative effects of radiation upon the child’s cognitive development. We need targeted therapeutics and to create those, we need to better understand the mechanisms driving ATRT.”

Led by Furnari and first author Alison Parisian, a graduate student in Funari’s lab, the team prompted the loss of SMARCB1 in human induced pluripotent stem cells, then directed the iPSCs to develop into neurons or into cerebral organoids — complexes of diverse nerve cells and glia that mimic functional aspects of the developing brain in miniature.

In doing so, they identified an interaction between the loss of SMARCB1 and neural differentiation pressure, which resulted in both a resistance to final differentiation and a defect in maintaining normal cell health that showed similarity to patient tumors.

“With this new information in hand,” said Parisian, “our plan is to use our ATRT model and look for therapeutic targets that will cause these tumors to fully differentiate and therefore stop growing, which could prove to be an effective future therapy for ATRT.”

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Materials provided by University of California – San Diego. Original written by Scott LaFee. Note: Content may be edited for style and length.



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