Immune Inflammation Pathways as Therapeutic Targets to Reduce Lethal Prostate Cancer in African American Men

SIMPLE SUMMARY: Men of African descent are twice as likely to die of prostate cancer than other men. While equal access to care is the key target to improve cancer survival, it is now known that there are differences in disease biology and risk factor exposure across population groups. These differences could be causatively linked to the existing prostate cancer health disparities. In this review, we will discuss the candidate role of inflammation and the immune response as contributing factors to the excessive burden of lethal prostate cancer among men of African ancestry. Furthermore, we will introduce the concept that these immunogenic vulnerabilities could be exploited to address the adverse outcomes experienced by these men. Lastly, we will summarize how these immunogenic and inflammatory differences could be targeted using current treatments to improve survival for men of African descent. ABSTRACT: Despite substantial improvements in cancer survival, not all population groups have benefitted equally from this progress. For prostate cancer, men of African descent in the United States and England continue to have about double the rate of fatal disease compared to other men. Studies suggest that when there is equal access to care, survival disparities are greatly diminished. However, notable differences exist in prostate tumor biology across population groups. Ancestral factors and disparate exposures can lead to altered tumor biology, resulting in a distinct disease etiology by population group. While equal care remains the key target to improve survival, additional efforts should be made to gain comprehensive knowledge of the tumor biology in prostate cancer patients of African descent. Such an approach may identify novel intervention strategies in the era of precision medicine. A growing body of evidence shows that inflammation and the immune response may play a distinct role in prostate cancer disparities. Low-grade chronic inflammation and an inflammatory tumor microenvironment are more prevalent in African American patients and have been associated with adverse outcomes. Thus, differences in activation of immune–inflammatory pathways between African American and European American men with prostate cancer may exist. These differences may influence the response to immune therapy which is consistent with recent observations. This review will discuss mechanisms by which inflammation may contribute to the disparate outcomes experienced by African American men with prostate cancer and how these immunogenic and inflammatory vulnerabilities could be exploited to improve their survival.