Cited by 152Vitamin D Research StudiesCancer Immunotherapy and BiomarkersGut microbiota and health

Vitamin D regulates microbiome-dependent cancer immunity

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Giampazolias, Evangelos, Pereira da Costa, Mariana, Lam, Khiem C., Lim, Kok Haw Jonathan, Cardoso, Ana, Piot, Cécile, Chakravarty, Probir, Blasche, Sonja +31 more·2024·Science

Abstract

A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D–induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis , which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.

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  • The microbiota produces B-series vitamins that support tissue homeostasis and immunosurveillance.

    “The microbiota synthesizes vitamins from the B series [76][77][78][79] that favor tissue homeostasis and immunosurveillance.”

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Authors
Giampazolias, E., Pereira da Costa, M., Lam, K. C., Lim, K. H. J., Cardoso, A., Piot, C., Chakravarty, P., Blasche, S., Patel, S., Biram, A., Castro-Dopico, T., Buck, M. D., Rodrigues, R. R., Poulsen, G. J., Palma-Duran, S. A., Rogers, N. C., Koufaki, M. A., Minutti, C. M., Wang, P., Vdovin, A., Frederico, B., Childs, E., Lee, S., Simpson, B., Iseppon, A., Omenetti, S., Kelly, G., Goldstone, R., Nye, E., Suárez-Bonnet, A., Priestnall, S. L., MacRae, J. I., Zelenay, S., Patil, K. R., Litchfield, K., Lee, J. C., Jess, T., Goldszmid, R. S., & Reis e Sousa, C.
Affiliations
  • The Francis Crick Institute (GB)
  • Immunobiology Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
  • National Cancer Institute (US)
  • University of Cambridge (GB)
  • University of Manchester (GB)
  • Frederick National Laboratory for Cancer Research (US)
  • Aalborg University Hospital (DK)
  • University College London (GB)
  • Experimental Histopathology, The Francis Crick Institute, London NW1 1AT, UK.
  • Royal Veterinary College (GB)
Corresponding author
  • Giampazolias, Evangelos
  • Lam, Khiem C.
  • Lim, Kok Haw Jonathan
  • Cardoso, Ana
  • Piot, Cécile
Venue
Science
Published
2024-04-26
Volume
384
Issue
6694
Pages
428-437
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W4395447498
Cited by
151
References
80
Citations by year
2026: 49 · 2025: 77 · 2024: 24 · 2023: 1
FWCI
45.44
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • VBN Forskningsportal (Aalborg Universitet) (publishedVersion, other-oa)
  • Research Explorer (The University of Manchester) (publishedVersion, other-oa)
  • PubMed Central (acceptedVersion, cc-by)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • The Francis Crick Institute (cc-by)
Funders
  • Wellcome Trust (CC2090, 216327, 106973/Z/15/Z, AdG 268670, 106973, 268670, /Z/15/Z, 216327/Z/19/Z)
  • Francis Crick Institute (CC2090, 106973/Z/15/Z, CC1061, 216327/Z/19/Z, CC2016, AdG 268670, CC1107, CC2219)
  • Frederick National Laboratory for Cancer Research
  • Cancer Research UK (A27412, 216327/Z/19/Z, C5759, 106973/Z/15/Z, CC2090, AdG 268670, C5759/A27412, 100001)
  • National Research Foundation (DNRF148)
  • Boehringer Ingelheim Fonds
  • Louis-Jeantet Foundation
  • Danmarks Grundforskningsfond (DNRF-148)
  • National Institutes of Health
  • Medical Research Council (MC_PC_24010, MC_UU_00025, 106973/Z/15/Z, 216327/Z/19/Z, MC_UU_00025/11, CC2090, AdG 268670)
  • National Cancer Institute
  • H2020 European Research Council (866028)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
vitamin D, gut microbiota, antitumor immunity, immune checkpoint inhibitors, Bacteroides fragilis, intestinal epithelial cells, transplantable tumors, immunomodulation, overall survival, commensal bacteria
MeSH terms
Gastrointestinal Microbiome, Immune Checkpoint Inhibitors, Animals, Bacteroides fragilis, Calcifediol, Diet, Female, Humans, Immunotherapy, Intestinal Mucosa, Male, Mice, Inbred C57BL, Neoplasms, Vitamin D, Vitamin D-Binding Protein, Cell Line, Tumor, Mice

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