Characterization of the Immune-Oncologic Profile of Lethal Prostate Cancer in African American Men
Posted April 14, 2021
Kosj Yamoah, M.D., Ph.D., H. Lee Moffitt Cancer Center
Prostate cancer (PCa) is the most common type of cancer among men after skin cancer, but the disease does not affect all races in the same manner. African American men are more than two times more likely to develop PCa and present with more advanced and aggressive disease, which is attributable to both biological and socio-economic factors. Specific to biological factors, Kosj Yamoah at the H. Lee Moffitt Cancer Center is focused on studying the genomic features of PCa tumors among men of different races in hopes of better understanding why African Americans are more susceptible to the disease.
Recent scientific advancements have led to the rapid emergence of highly effective immunotherapies for different cancers. But unlike other malignancies, the FDA-approved immunotherapies for PCa remain limited. The “landscape” or immune cells capable of being triggered to attack PCa cells are an important factor in effective immunotherapies, and while previous studies have looked at the immune landscape of PCa in European American men, they have lacked validation among their African American counterparts. With funding from a FY18 Health Disparity Award, Dr. Yamoah has shown that prostate tumors from African American men have higher immune content and that several immune-related genomic markers are dysregulated. Furthermore, he found that African American men with PCa have an immunosuppressive tumor immune microenvironment (TIME), which helps tumors suppress the immune system and escape from immune surveillance, leading to subsequent tumor growth. Consequently, immune mediators may play a major role in the initiation and progression of PCa in African American men.
These findings demonstrate that African American men with PCa manifest a unique immune repertoire and these immune-oncologic differences can aid in new approaches to treatment. Dr. Yamoah and his laboratory are working to further understand the mechanism and potential therapeutic benefit of combining immune modulators to disrupt the TIME for therapeutic gain in African American men with PCa. Ultimately, he hopes these findings will help to guide treatment strategies for African American men and reduce PCa health disparities.
Heatmap of intergene correlation showing a unique cluster of immune-oncologic genes were observed in African American men. Gene set enrichment analysis (GSEA) revealed immune biologic signatures that were enriched for major pathways including cytokine signaling, IFN signaling, and signaling by ILs including IL4 and IL13.
Shivanshu Awasthi, Anders E. Berglund, Julieta Abraham-Miranda, Robert J. Rounbehler, Kevin H Kensler, Amparo N Serna, Adriana C Vidal, Sungyong You, Michael R Freeman, Elai Davicioni, Yang Liu, Jeffrey R. Karnes, Eric A. Klein, Robert B Den, Bruce J. Trock, Joshua D. Campbell, David J Einstein, Raavi Gupta, Steven P. Balk, Priti Lal, Jong Y. Park, John L Cleveland, Timothy R. Rebbeck, Stephen J. Freedland and Kosj Yamoah. Comparative genomics reveals distinct immune-oncologic pathways in African American men with prostate cancer. Clin Cancer Research. 2020 Oct 9
Last updated Wednesday, April 14, 2021