Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression

Arianna Calcinotto, Arianna Brevi, Marta Chesi, Roberto Ferrarese, Laura Garcia Perez, Matteo Grioni, Shaji Kumar, Victoria M. Garbitt, Meaghen E. Sharik, Kimberly J. Henderson, Giovanni Tonon, Michio Tomura, Yoshihiro Miwa, Enric Esplugues, Richard A. Flavell, Samuel Huber, Filippo Canducci, Vincent S. Rajkumar, P. Leif Bergsagel, Matteo Bellone

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The gut microbiota has been causally linked to cancer, yet how intestinal microbes influence progression of extramucosal tumors is poorly understood. Here we provide evidence implying that Prevotella heparinolytica promotes the differentiation of Th17 cells colonizing the gut and migrating to the bone marrow (BM) of transgenic Vk*MYC mice, where they favor progression of multiple myeloma (MM). Lack of IL-17 in Vk*MYC mice, or disturbance of their microbiome delayed MM appearance. Similarly, in smoldering MM patients, higher levels of BM IL-17 predicted faster disease progression. IL-17 induced STAT3 phosphorylation in murine plasma cells, and activated eosinophils. Treatment of Vk*MYC mice with antibodies blocking IL-17, IL-17RA, and IL-5 reduced BM accumulation of Th17 cells and eosinophils and delayed disease progression. Thus, in Vk*MYC mice, commensal bacteria appear to unleash a paracrine signaling network between adaptive and innate immunity that accelerates progression to MM, and can be targeted by already available therapies.

Original languageEnglish (US)
Article number4832
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Calcinotto, A., Brevi, A., Chesi, M., Ferrarese, R., Garcia Perez, L., Grioni, M., Kumar, S., Garbitt, V. M., Sharik, M. E., Henderson, K. J., Tonon, G., Tomura, M., Miwa, Y., Esplugues, E., Flavell, R. A., Huber, S., Canducci, F., Rajkumar, V. S., Bergsagel, P. L., & Bellone, M. (2018). Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression. Nature communications, 9(1), [4832]. https://doi.org/10.1038/s41467-018-07305-8