Tumor Microbiome Composition Influences Pancreatic Cancer Survival

Gut microbiota can regulate immune responses beyond the gut, and recent studies suggest that gut microbiota may mediate chemotherapeutic and immunotherapeutic responses. Riquelme, Zhang, and colleagues investigated the role of tumor microbial populations in the survival of patients with pancreatic ductal adenocarcinoma (PDAC). Tumor microbial diversity was characterized in two independent cohorts of patients with surgically resected PDAC who were long-term survivors (LTS) or short-term survivors (STS). Compared with STSs, LTSs exhibited increased microbial diversity and enrichment of district bacterial species that correlated with overall survival. Furthermore, higher densities of CD3⁺ and CD8⁺ T cells and increased numbers of granzyme B⁺ cells were found in LTS tumors, and CD8⁺ T-cell density correlated with the top three enriched bacterial genera in LTSs. Intratumoral microbiome composition also correlated with differential enrichment of metabolic pathways. Comparison of matched gut, tumor, and adjacent normal tissue microbiomes from three patients with PDAC showed that the gut microbiome represents approximately 25% of the tumor microbiome and is absent in adjacent normal tissue. Fecal microbial transplantation (FMT) from STSs to mice previously treated with antibiotics resulted in the presence of bacteria of human origin in both murine gut and tumor. FMT from LTSs, STSs, or healthy controls showed that mice receiving FMT from LTSs exhibited enhanced survival and increased levels of CD8⁺ T cells and activated CD8⁺ T cells, whereas mice receiving FMT from STSs exhibited increased levels of CD4⁺FOXP3⁺ and myeloid-derived tumor suppressor cells, and T-cell depletion blocked the antitumor effect induced by FMT from LTSs. Collectively, these results suggest that gut microbiota can colonize pancreatic tumors, change intratumoral bacterial composition, recruit and activate CD8⁺ T cells, and prolong survival of patients with PDAC. Therefore, determining the tumor microbiome of patients with PDAC may serve as a prognostic tool, and FMT from LTS patients may have therapeutic potential.

Riquelme E, Zhang Y, Zhang L, Montiel M, Zoltan M, Dong W, et al. Tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell 2019;178:795–806.

• ©2019 American Association for Cancer Research.