Author
Listed:
- Arianna Calcinotto
(IRCCS San Raffaele Scientific Institute
Oncology Institute of Southern Switzerland)
- Arianna Brevi
(IRCCS San Raffaele Scientific Institute
Vita-Salute San Raffaele University)
- Marta Chesi
(Mayo Clinic Arizona)
- Roberto Ferrarese
(IRCCS San Raffaele Scientific Institute)
- Laura Garcia Perez
(Molekulare Immunologie und Gastroenterologie, Universitätsklinikum Hamburg–Eppendorf)
- Matteo Grioni
(IRCCS San Raffaele Scientific Institute)
- Shaji Kumar
(Mayo Clinic Rochester)
- Victoria M. Garbitt
(Mayo Clinic Arizona)
- Meaghen E. Sharik
(Mayo Clinic Arizona)
- Kimberly J. Henderson
(Mayo Clinic Rochester)
- Giovanni Tonon
(IRCCS San Raffaele Scientific Institute)
- Michio Tomura
(Osaka Ohtani University)
- Yoshihiro Miwa
(University of Tsukuba)
- Enric Esplugues
(School of Medicine, and Howard Hughes Medical Institute Yale University)
- Richard A. Flavell
(School of Medicine, and Howard Hughes Medical Institute Yale University)
- Samuel Huber
(Molekulare Immunologie und Gastroenterologie, Universitätsklinikum Hamburg–Eppendorf)
- Filippo Canducci
(IRCCS San Raffaele Scientific Institute
University of Insubria)
- Vincent S. Rajkumar
(Mayo Clinic Rochester)
- P. Leif Bergsagel
(Mayo Clinic Arizona)
- Matteo Bellone
(IRCCS San Raffaele Scientific Institute)
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.
Suggested Citation
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 Ton, 2018.
"Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression,"
Nature Communications, Nature, vol. 9(1), pages 1-13, December.
Handle:
RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07305-8
DOI: 10.1038/s41467-018-07305-8
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