{
  "abstract": "Background Prostate cancer (PCa) exemplifies the pronounced ethnic disparities observed across multiple cancer types. Men of African ancestry exhibit a 60% higher lifetime incidence and double the mortality rate compared to men of European descent. This disproportionate burden necessitates in-depth investigation of PCa biology, with a focus on the tumour microbiome and the tumour immune microenvironment (TiME) across diverse ethnic groups.Methods A UK cohort of 114 formalin-fixed paraffin embedded (FFPE) radical prostatectomy tissues from patients of different ethnicities was studied. Prostate tissues underwent whole-genome single nucleotide polymorphism genotyping to accurately establish patient ancestry, in addition to self-described ethnicity and patient clinical data. Dissection of pathologist-annotated tumour regions allowed for extraction of genomic DNA from tumour-enriched and adjacent-normal regions for shotgun metagenomic sequencing to enable microbial profiling within distinct intraprostatic niches. A comprehensive characterization of the TiME in 12 PCa patients of different ethnicities, was performed using the spatial biology technology MACSima™ imaging cyclic staining (MICS) (Miltenyi Biotec) utilizing a 118-plex immuno-oncology panel and specific prostate cancer markers of interest. Analysis of tumour-core, invasive-margin and distant-normal prostate regions was performed using MACS® iQ View Software for in-depth profiling of cell types, states, and cellular neighbourhoods within the intra-prostatic niches of Black-African, Black-Caribbean, Asian and White men.Results Metagenomic analysis revealed the presence of Cutibacterium acnes in prostatectomy tissues across all ethnic groups with a significantly increased abundance within tumour enriched areas relative to normal prostate. The opportunistic pathogen Moraxella osloensis was detected in both Black and Asian normal and tumour samples however was absent from the prostate microbiome of White patients. In Black patients, several bacterial species were identified in both normal and tumour samples, including Cloacibacterium caeni, Enterococcus faecium, Mycolicibacterium peregrinum and Pseudomonas chengduensis. Having validated a comprehensive 118-marker immunophenotyping panel for multiplexed imaging, at present we are exploring the interrelationships between ethnicity, PCa-associated bacteria and the TiME.Conclusions To our knowledge, ours is the first study to comprehensively profile both the tumour microbiome and the TiME within an ethnically-diverse cohort of PCa patients. The presence of Cutibacterium acnes across PCa from all ethnicities further supports a role for this bacteria in establishing PCa immunosuppression, which could favour the colonization of ethnic-specific opportunistic bacteria. By understanding these complex microbiome-PCa TiME interactions, our work will impact the development of novel therapeutic strategies to overcome ethnic disparities in PCa clinical outcomes.Ethics Approval This study was approved by the Research Ethics Committee (REF: 23/SC/0051, IRAS ID: 316347).",
  "authors": [
    {
      "affiliations": [
        "University of Surrey, Guildford, Surrey, UK"
      ],
      "name": "James R Thetford"
    },
    {
      "affiliations": [
        "Miltenyi Biotec, Walthan, MA, USA"
      ],
      "name": "Eric C DiBiasio"
    },
    {
      "affiliations": [
        "Miltenyi Biotec, Woking, Surrey, UK"
      ],
      "name": "Jak Grimes"
    },
    {
      "affiliations": [
        "Miltenyi Biotec, Bergisch Gladbach, Germany"
      ],
      "name": "Katrin Schönborn"
    },
    {
      "affiliations": [
        "Miltenyi Biotec, Bergisch Gladbach, Germany"
      ],
      "name": "Stefan Eulitz"
    },
    {
      "affiliations": [
        "The Royal Marsden NHS Foundation Trust, London, UK"
      ],
      "name": "Elizabeth Bancroft"
    },
    {
      "affiliations": [
        "Institute of Cancer Research, London, UK"
      ],
      "name": "Rosalind Eeles"
    },
    {
      "affiliations": [
        "The North Bristol NHS Foundation Trust, Bristol, UK"
      ],
      "name": "Jonathan Aning"
    },
    {
      "affiliations": [
        "The Royal Surrey NHS Foundation Trust, Guildford, Surrey, UK"
      ],
      "name": "Ben Haagsma"
    },
    {
      "affiliations": [
        "University of Surrey, Guildford, Surrey, UK"
      ],
      "name": "Lisiane B Meira"
    },
    {
      "affiliations": [
        "University of Surrey, Guildford, Surrey, UK"
      ],
      "name": "Nicola E Annels"
    }
  ],
  "title": "1148 Dissecting the prostate cancer microbiome and immune microenvironment to understand ethnic disparities in clinical outcomes",
  "uid": "4f9fb53c-0e4b-53fb-a2ef-5b72e5db378f"
}