Researchers Offer Evidence That Prostate Cancer Biology May Differ by Racial Ancestry

By: Celeste L. Dixon
Posted: Tuesday, August 30, 2022

New research findings on the immunomodulatory molecule called B7 homolog 3, or B7-H3, add to evidence that prostate cancer in men of African ancestry may have a distinct tumor biology. The data have potentially important clinical implications for immunotherapy in this population, according to Tamara L. Lotan, MD, of Johns Hopkins University School of Medicine, Baltimore, and colleagues in Cancer. B7-H3 is part of the B7 superfamily, which includes PD-L1, and was already known to be highly expressed in prostate cancer.

Studying the molecular and immune microenvironment correlates of B7-H3 expression could help to guide trial design and interpretation, explained the team. “Immunotherapies—antibodies, antibody-drug conjugates, and chimeric antigen receptor T cells—targeting B7-H3 are currently in clinical trials,” they wrote. And, as far as they knew, their study may be the first “to examine B7-H3 expression in prostate cancer from a racially diverse cohort with genetic ancestry annotations, the first to correlate B7-H3 expression with quantified immune cell densities, and the first to examine the expression of B7-H3 in paired samples before and after intensive hormonal therapy.”

Dr Lotan and co-investigators described four significant findings from their research:

In self-identified Black patients with primary prostate cancer, B7-H3 protein expression was significantly lower than in non-Black patients; the expression was inversely correlated with the percentage of African ancestry.
This association with race was independent of the significant association of B7-H3 protein expression with ERG/ETS and PTEN status.
B7-H3 messenger RNA expression—but not B7-H3 protein expression—was significantly correlated with regulatory (FOXP3-positive) T-cell density.
Androgen receptor activity scores were significantly correlated with B7-H3 messenger RNA expression. Also, neoadjuvant intensive hormonal therapy was associated with a significant decrease in B7-H3 protein expression.

Disclosure: The study authors’ disclosure information can be found at acsjournals.onlinelibrary.wiley.com.

Cancer