The hidden microbiome within: microbial architecture of the pancreatic cancer microenvironment

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense desmoplastic and immunosuppressive tumor microenvironment that limits immune surveillance and therapeutic delivery. Emerging evidence indicates that PDAC harbors low-biomass but biologically relevant intratumoral microbial communities. This review synthesizes current evidence on the existence, spatial localization, functional relevance, and translational implications of the intratumoral microbiome in PDAC. A narrative literature review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar to identify English-language studies on the PDAC intratumoral microbiome, tumor-resident bacteria and fungi, tumor microenvironment interactions, spatial and single-cell analyses, contamination control, and therapeutic response. Tumor-resident bacterial and fungal communities in PDAC may influence immune reprogramming, fibro-inflammatory signaling, metabolic stress responses, postoperative survival, and therapy response. These microbes interact with myeloid cells, dendritic cells, T cells, cancer-associated fibroblasts, stromal architecture, and hypoxic niches. Spatial and single-cell studies suggest that microbial signals align with distinct tumor niches, supporting localized microbe–host crosstalk. The intratumoral microbiome is emerging as a non-genetic regulator of PDAC biology. Integrated microbial, immune, stromal, and metabolic profiling may support future precision-oncology strategies. Not applicable.