Table 1 Multiple bacterial taxa have been investigated for their impact on PDAC progression.
From: Intratumoral microbiome and pancreatic cancer: an enabling hallmark and path to novel treatments?
Taxon | Clinical association | Affected hallmark | Mechanistic impact | Refer-ences |
|---|---|---|---|---|
Fusobacterium nucleatum | Associated with PDAC and short survival | ↑ Tumor-promoting inflammation ↑ Immune evasion ↑ Sustained proliferation ↑ Metastasis | Secretion of cytokines (GM-CSF, CXCL1, IL-8, MIP-3α) boost PDAC cell proliferation, migration and invasiveness | [6] |
↑ Sustained proliferation | Stimulation of the Ku70/p53 pathway, increasing proliferation | [5] | ||
↑ Immune evasion | Secretion of CXCL1, resulting in recruitment of immunosuppressive myeloid-derived suppressor cells and reduction of CD8 + T cell infiltration | [10] | ||
↑ Genomic instability | Induction of double strand breaks and upregulation of checkpoint kinase 2 | |||
Porphyromonas gingivalis (P. gingivalis) | Associated with PDAC and precursor lesions | ↑ Phenotypic plasticity ↑ Cell death resistance | Increased expression of SOX9, CK19; protection against ROS | [21] |
↑ Sustained proliferation | Development of PanIN through increase of proliferation marker expression | [48] | ||
↑ Tumor-promoting inflammation | Inflammation by expression of gingipain proteases | [15] | ||
bacteria expressing cytidine deaminase (particularily Gammaproteo-bacteria, Aggregatibacter actinomycetem-comitans, P. gingivalis, Streptococcus mutans) | Associated with short survival after chemotherapy | ↑ Cell death resistance | Both long- and short-form cytidine deaminase metabolize gemcitabine, reducing treatment efficacy | [24] |
gram negative bacteria expressing LPS | Associated with short survival | ↑ Tumor-promoting inflammation | Enhance PDAC viability through induction of the inflammasome in macrophages and PDAC cells, increasing the expression of IL-1ß and TNFα | [17] |
diverse microbiome (also modulated by fecal matter transplantation) | Associated with long term survival | ↓ Immune evasion | Modulates tumor growth and immune infiltration | [22] |
lactic acid bacteria (particularily Lactobacillus species) | Associated with long term survival | ↓ Immune evasion | Reversal of P. gingivalis induced proliferation and inflammation;decrease of Gal-3 and PD-L1 expression on cancer cells | [48] |
Escherichia coli (pks+) | No clear association | ↑ Genomic instability | Express colibactin, which can induce DNA damage | [3] |
Helicobacter pylori | No clear association | ↑ Tumor-promoting inflammation ↑ Sustained proliferation | Increases levels of IL-8, VEGF | [14] |
Pseudomonas aeruginosa | No clear association | ↓ Sustained proliferation ↓ Cell death resistance | Produces a mannose-sensitive hemagglutinin lectin, which induces cell cycle arrest and apoptosis through inhibition of the EGFR/Akt/ERK signaling pathway | [20] |
