Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment

Noriho Iida, Amiran Dzutsev, C. Andrew Stewart, Loretta Smith, Nicolas Bouladoux, Rebecca A. Weingarten, Daniel A. Molina, Rosalba Salcedo, Timothy Back, Sarah Cramer, Ren Ming Dai, Hiu Kiu, Marco Cardone, Shruti Naik, Anil K. Patri, Ena Wang, Francesco M. Marincola, Karen M. Frank, Yasmine Belkaid, Giorgio TrinchieriRomina S. Goldszmid

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Abstract

The gut microbiota influences both local and systemic inflammation. Inflammation contributes to development, progression, and treatment of cancer, but it remains unclear whether commensal bacteria affect inflammation in the sterile tumor microenvironment. Here, we show that disruption of the microbiota impairs the response of subcutaneous tumors to CpG-oligonucleotide immunotherapy and platinum chemotherapy. In antibiotics-treated or germ-free mice, tumor-infiltrating myeloid-derived cells responded poorly to therapy, resulting in lower cytokine production and tumor necrosis after CpG-oligonucleotide treatment and deficient production of reactive oxygen species and cytotoxicity after chemotherapy. Thus, optimal responses to cancer therapy require an intact commensal microbiota that mediates its effects by modulating myeloid-derived cell functions in the tumor microenvironment. These findings underscore the importance of the microbiota in the outcome of disease treatment.

Original languageEnglish
Pages (from-to)967-970
Number of pages4
JournalScience
Volume342
Issue number6161
DOIs
Publication statusPublished - 1 Jan 2013

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Cite this

Iida, N., Dzutsev, A., Stewart, C. A., Smith, L., Bouladoux, N., Weingarten, R. A., Molina, D. A., Salcedo, R., Back, T., Cramer, S., Dai, R. M., Kiu, H., Cardone, M., Naik, S., Patri, A. K., Wang, E., Marincola, F. M., Frank, K. M., Belkaid, Y., ... Goldszmid, R. S. (2013). Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science, 342(6161), 967-970. https://doi.org/10.1126/science.1240527