The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression
By S. Pushalkar, Mautin Hundeyin, Donnele Daley, C. Zambirinis, Emma Kurz, Ankita Mishra, Navyatha Mohan, Berk Aykut, Mykhaylo Usyk, Luisana Torres and 23 more. Cancer Discovery, 2018
1,139 citations recorded by the source corpus.
We found that the cancerous pancreas harbors a markedly more abundant microbiome compared to normal pancreas in both mice and humans, while select bacteria are differentially increased in the tumorous pancreas compared to gut. Ablation of the microbiome protects against pre-invasive and invasive PDA, whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor-protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting Th1 differentiation of CD4+ T cells and CD8+ T cell activation. Bacterial ablation also enabled efficacy for checkpoint-targeted immunotherapy by upregulating PD-1 expression. Mechanistically, the PDA microbiome generated a tolerogenic immune program by differentially activating select toll-like receptors in monocytic cells. These data suggest that endogenous microbiota promote the crippling immune-suppression characteristic of PDA and that the microbiome has potential as a therapeutic target in the modulation of disease progression.
Subfields: Biotechnology, Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/aa07cb3b515cda1ea2814cb9630b114c9d673ec5
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Citations in the corpus
- Interaction between microbiota and immunity in health and disease (2020, background): “For example, intra-tumor microbiota in pancreatic adenocarcinoma (PDAC) in mice and humans promotes carcinogenesis through induction of a tolerogenic immune program, including suppressive differentiation in monocytes via selective TLRs and T cell anergy.(197) In addition, the presence of Gammaproteo”
- Hallmarks of Cancer: New Dimensions. (2022, background): “Microbiota have been similarly detected in genetically engineered de novo mouse models of lung and pancreas cancer, and their absence in germ-free mice and/or their abrogation with antibiotics can demonstrably impair tumorigenesis, functionally implicating the tumor microbiome as an enabler of tumor”
- Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes (2019, background): “detected specific gut and tumor microbiome in murine models of PDAC, suggesting potential bacterial translocation from the intestinal tract into the peritumoral milieu (Pushalkar et al., 2018).”