Abstract C117: Integrative multi-omics profiling in patients of African descent diagnosed with prostate cancer reveals distinct tumor-promoting immunosuppressive niches at a single-cell level and spatial resolution

Abstract In the United States and globally, prostate cancer (PCa) mortality rates are the highest among men of African descent. 24% of the disparities in PCa remains even when controlled for access to care and stage at presentation. Moreover, the tumor microenvironment plays an essential role in tumor progression, aggressiveness, therapeutic response, and patient outcomes. Additionally, the association of the genomic findings with patient ancestry and other characteristics, such as tumor biology and transcriptomic alterations, remains poorly understood. Here, we performed a multi-Omics approach (N=447) to unravel the complexity of tumor heterogeneity and understand disease progression 70%) Ancestry with either Yoruba (Nigeria) and/or Bantu subpopulation in the Sub-Saharan area. Additionally, high African Ancestry patients are diagnosed at a younger age and show advanced pathology stages compared to patients with European Ancestry. AAM of Yoruba descent expresses significantly higher immune-inflammatory signatures (STAT/IFNG-signaling pathway) compared to the Nigerian-Yoruba subpopulation. Our scRNA-Seq analysis shows that AAM has suppressive myeloid cells infiltrate within the tumor cells. The infiltrations of these cells change with age, Gleason Grade, and pathology stage. Moreover, AAM-tumor cells (scATAC-Seq) have increased open Chromatin accessibility with STAT motifs enrichment (p-value;0.0001), which could be the driver regulators of the immune-suppressive signature as well as influence the upregulation of STAT/IFNG signature within African Ancestry patients. Our study provides new insight into how genetic ancestry impacts immune signatures in AAM/African and contributes to PCa racial disparities. Citation Format: Isra Elhussin, Ezra Baraban1, Ashley Kiemen, Tamara L Lotan, Cathy Handy Marshall, Emmanuel Antonarakis, Moray J Campbell, Melissa Davis, Michael Dixon, Isaac Kim, Stefan Ambs, Rick Kittles, Adam B Murphy, Clayton Yates. Integrative multi-omics profiling in patients of African descent diagnosed with prostate cancer reveals distinct tumor-promoting immunosuppressive niches at a single-cell level and spatial resolution abstract. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C117.