Genomic analysis identifies immune-oncologic differences in prostate tumors of African American men

Immune-oncologic differences in tumor cells may contribute to prostate cancer disparities between African American men and European American men, according to an analysis published in Clinical Cancer Research.^1,2

The analysis was conducted by researchers at Moffitt Cancer Center, who hope their findings can help deliver precision medicine to African American men, an underserved population that faces higher prostate cancer incidence and mortality rates than European American men.

Kosj Yamoah, MD, PhD

“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,” Kosj Yamoah, MD, PhD, associate member and director of cancer disparities research in the departments of Radiation Oncology and Cancer Epidemiology at Moffitt Cancer Center, stated in a press release. “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.”

Using the Decipher Genomic Resource Information Database (GRID), researchers at Moffitt examined whole transcriptome data from 1173 radiation-naïve prostatectomy samples. The investigators selected transcriptomic expressions of 1260 immune-specific genes to identify immune-oncologic differences between African American (AAM) and European American (EAM) prostate tumors.

The analysis found that the AAM prostate tumors had significant enrichment of major immune-oncologic pathways that can facilitate the proliferation and spread of tumors cells. The pathways included pro-inflammatory cytokines, IFN-α, IFN-γ and TNF-α signaling, interleukins, and EMT.

The researchers specifically found that expression levels of 6 genes were consistently higher for the AAM tumors compared with the EAM tumors.One of these pro-inflammatory genes overexpressed in AAM tumors was IFITM3, which is linked to a significantly increased risk of biochemical recurrence and metastasis. In both discovery (HR, 2.30; P = .01) and validation (HR, 2.42; P = 0.0001), IFITM3 predicted for increased risk of biochemical recurrence selectively for AAM, the researchers noted.

Compared to the tumor microenvironment (TME) in EAM tumors, the AAM TME had a higher total immune content score at 37.8% versus 21.9% (P = .003). DNA damage repair was also lower in AAM tumors.

The immune-oncologic differences in AAM prostate tumors suggest that African American men might respond well to immunotherapy, according to the researchers. The analysis also showed the AAM tumors were more genomically radiosensitive compared to EAM tumors, suggesting radiotherapy might be more effective in these patients, as well.

“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,” stated 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.”

References

1. Genomic Differences May Be Key to Overcoming Prostate Cancer Disparities Among African American Men. Moffitt Cancer Center. Published online October 21, 2020. https://bit.ly/2Thkfv5. Accessed October 22, 2020.

2. Shivanshu A, Berglund AE, Abraham-Miranda J, et al. Comparative genomics reveals distinct immune-oncologic pathways in African American men with prostate cancer [published online ahead of print October 9, 2020]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-20-2925