Tumor microbiome links cellular programs and immunity in pancreatic cancer

Cancer Cell. 2022 Oct 10;40(10):1240-1253.e5. doi: 10.1016/j.ccell.2022.09.009.


Microorganisms are detected in multiple cancer types, including in putatively sterile organs, but the contexts in which they influence oncogenesis or anti-tumor responses in humans remain unclear. We recently developed single-cell analysis of host-microbiome interactions (SAHMI), a computational pipeline to recover and denoise microbial signals from single-cell sequencing of host tissues. Here we use SAHMI to interrogate tumor-microbiome interactions in two human pancreatic cancer cohorts. We identify somatic-cell-associated bacteria in a subset of tumors and their near absence in nonmalignant tissues. These bacteria predominantly pair with tumor cells, and their presence is associated with cell-type-specific gene expression and pathway activities, including cell motility and immune signaling. Modeling results indicate that tumor-infiltrating lymphocytes closely resemble T cells from infected tissue. Finally, using multiple independent datasets, a signature of cell-associated bacteria predicts clinical prognosis. Tumor-microbiome crosstalk may modulate tumorigenesis in pancreatic cancer with implications for clinical management.

Keywords: cancer biology; cancer genomics; gene expression; immunity; microbiome; oncogenesis; single cell sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria
  • Carcinogenesis
  • Cell Transformation, Neoplastic
  • Humans
  • Lymphocytes, Tumor-Infiltrating
  • Microbiota*
  • Pancreatic Neoplasms* / genetics