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Cited by 223Multiple Myeloma Research and TreatmentsGut microbiota and healthT-cell and B-cell Immunology

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

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Calcinotto, Arianna, Brevi, Arianna, Chesi, Marta, Ferrarese, Roberto, Garcia Perez, Laura, Grioni, Matteo, Kumar, Shaji, Garbitt, Victoria M. +12 more·2018·Nature Communications
DOI 10.1038/s41467-018-07305-8PMC PMC6277390
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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.

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  • Several patterns of immune dysregulation have been reported in MGUS and SMM using single cell RNA sequencing.

    “Several patterns of dysregulation have been reported using single cell RNA sequencing.82,83,91-93”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [93]

    The Discussion (page not provided) describes Th17-cell enrichment in some MGUS-SMM patients and links higher bone-marrow IL-17 in SMM to faster progression. That supports an immune alteration, but the paper does not report several patterns of dysregulation identified by single-cell RNA sequencing; its Methods describe flow cytometry and other approaches instead. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
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.
Affiliations
  • Institute of Oncology Research (CH)
  • Vita-Salute San Raffaele University (IT)
  • Mayo Clinic in Arizona (US)
  • IRCCS Ospedale San Raffaele (IT)
  • Mayo Clinic (US)
  • Osaka Ohtani University (JP)
  • University of Tsukuba (JP)
  • Howard Hughes Medical Institute (US)
  • University Medical Center Hamburg-Eppendorf (DE)
  • University of Insubria (IT)
Corresponding author
Bellone, Matteo
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-12-03
Volume
9
Issue
1
Pages
4832-4832
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-018-07305-8
PMC
PMC6277390
OpenAlex
W2901497217
Cited by
223
References
8
Citations by year
2026: 20 · 2025: 30 · 2024: 29 · 2023: 36 · 2022: 27 · 2021: 44 · 2020: 23 · 2019: 13
FWCI
14.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
  • IrInSubria (University of Insubria) (submittedVersion)
  • Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
  • Terrestrial Environment Research Center (University of Tsukuba) (submittedVersion, cc-by-nc-nd)
Funders
  • Amgen
  • Associazione Italiana per la Ricerca sul Cancro (5×1000)
  • Fondazione Italiana per la Ricerca sul Cancro
  • Japan Society for the Promotion of Science (16H01630, 16H05087, 15H05935)
  • National Cancer Institute (CA190045, CA168762, CA186781, R01CA190045, R01CA195688, R01CA234181, R01CA168762, P50CA186781)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
gut microbiota, multiple myeloma, Th17 cells, IL-17, eosinophils, bone marrow, smoldering multiple myeloma, STAT3 phosphorylation, plasma cells, IL-17RA, IL-5, disease progression, commensal bacteria
MeSH terms
Gastrointestinal Microbiome, Animals, Bone Marrow, Cell Differentiation, Cell Movement, Eosinophils, Humans, Mice, Inbred C57BL, Mice, Transgenic, Multiple Myeloma, Mice, Knockout, Disease Progression, Prevotella, Interleukin-17, Th17 Cells

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