Patient-derived pancreatic tumor bacteria exhibit oncogenic properties and are recognized by MAIT cells in tumor spheroids.

INTRODUCTION

Tumor-residing microbiota poses a new challenge in cancer progression and therapy; however, the functional behavior of patient tumor-derived microbes remains poorly understood. We previously reported the presence of tumor microbiota in intraductal papillary mucinous neoplasms (IPMNs), which are precursors of pancreatic cancer.

METHODS

We examined the metabolic and pathogenic potential of clinical microbiota strains obtained from IPMN tumors using various pancreatic cell lines and 3D spheroid models.

RESULTS

Our findings revealed that several strains from IPMNs with invasive cancer or high-grade dysplasia, such as E. cloacae, E. faecalis, and K. pneumoniae, induced a cancer metabolite signature in human pancreatic cells when infected ex vivo. Bacterial invasiveness was significantly correlated with DNA damage in spheroids derived from normal and tumor-derived pancreatic cells, particularly in strains derived from advanced neoplasia IPMN and under hypoxic conditions. Additionally, microbial metabolites activate human mucosal-associated invariant T (MAIT) cells and restrict the infection, both extra- and intracellularly, in hypoxic tumor conditions and in synergy with antibiotics.

DISCUSSION: Immune sensing of tumor microbiota metabolites may have clinical implications in cancer management.