Single cell analysis of circulating peripheral blood mononuclear cells in African American men with prostate cancer and their association with lethal disease

Authors

• HE Gichini
• TA Hoeltermann
• M Joe
• E Towalid
• M Chea
• Y Quiawiah
• M Kopah
• L Marron
• M Gboue
• B Dighero-Kemp
• J Kuhn
• P Chandrasekaran
• IB Maljkovic

Abstract

Prostate cancer is a leading cause of cancer-related deaths among men in the US and affects African American (AA) men more so than other men. We and others previously described a distinct tumor immunobiology in AA, which is associated with lethal prostate cancer. In this study, we sought to investigate the composition of circulating peripheral blood mononuclear cells (PBMCs) in AA and European American (EA) prostate cancer patients and their association with race and lethal prostate cancer. We obtained high-quality RNA-sequencing data for 277642 single cells representing circulating PBMCs from 59 AA and EA men. In the analysis, being AA patients associated with increased abundance of exhausted CD8+T cells and higher numbers of tumor-associated macrophages, whereas metallothionine-expressing macrophages were decreased in these men. Gene signatures indicative of T cell exhaustion were generally elevated in AA PBMCs while T cell effector function features were decreased. Within the myeloid cell population, cytokine and NFKB signatures were more prevalent in AA than EA. This gene signature pattern that we observed in AA patients also associated with lethal prostate cancer, namely the T cell exhaustion and elevated cytokine gene signatures, pointing to potential clinical implications. Lastly, the interferon-induced transmembrane protein (IFITM3), interferon alpha inducible protein (IFI6), cysteine rich protein-1 (CRIP1), and the RAC family small GTPase2 (RAC2) were notably upregulated in AA patients. In summary, we show that circulating immune cell populations and associated gene signatures differ between men of African and European descent. Those elevated in AA patients correlated with lethal prostate cancer.

Scientific Focus Area: Health Disparities

This page was last updated on Monday, September 25, 2023