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Tumour microenvironment

Bacterial balance affects cancer treatment

Nature Reviews Cancer volume 14, page 11 (2014)Cite this article

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Iida et al. specifically asked how perturbing the commensal bacteria populations in the gut by antibiotics affects tumours that are treated with immunotherapy or chemotherapy. They pretreated mice with ABX, which is a broad-spectrum antibiotic cocktail consisting of vancomycin, imipenem and neomycin, prior to inoculating the mice with subcutaneous tumours and then treating them with immunotherapy or chemotherapy.

Mice were treated with a combination immunotherapy consisting of CpG oligonucleotides, a ligand to Toll-like receptor 9 (TLR9) and inhibitory interleukin-10 receptor antibodies to activate Toll-like receptors on myeloid cells and induce tumour necrosis factor (TNF) production. Mice that were pretreated with ABX had a reduced response to this immunotherapy: there was less of an effect on tumour growth and a lower proportion of mice survived compared with mice that were not treated with ABX. The authors showed that ABX reduced TNF production: mice that lacked TNF phenocopied mice that were treated with ABX. These effects were dependent on the decreased bacterial load that was induced by ABX, as germ-free mice had a similarly attenuated response to immunotherapy. Moreover, in ABX-treated mice, TNF expression and tumour necrosis could be rescued by oral treatment with bacterial lipopolysaccharide (LPS), which is an immune cell stimulant.

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References

  1. Iida, N. et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342, 967–970 (2013)

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  2. Viaud, S. et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342, 971–976 (2013)

    Article  CAS  Google Scholar 

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  1. Isabel Lokody
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Lokody, I. Bacterial balance affects cancer treatment. Nat Rev Cancer 14, 11 (2014). https://doi.org/10.1038/nrc3658

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