The Francis Crick Institute
VitD_Science_v3.9_Final_unformatted_headings.pdf (3.21 MB)

Vitamin D regulates microbiome-dependent cancer immunity.

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journal contribution
posted on 2024-05-08, 10:34 authored by Evangelos Giampazolias, Mariana Pereira da Costa, Khiem C Lam, Kok Haw Jonathan Lim, Ana Cardoso, Cécile Piot, Probir Chakravarty, Sonja Blasche, Swara Patel, Adi Biram, Tomas Castro-Dopico, Michael D Buck, Richard R Rodrigues, Gry Juul Poulsen, Susana A Palma-Duran, Neil C Rogers, Maria A Koufaki, Carlos M Minutti, Pengbo Wang, Alexander Vdovin, Bruno Frederico, Eleanor Childs, Sonia Lee, Ben Simpson, Andrea Iseppon, Sara Omenetti, Gavin Kelly, Robert Goldstone, Emma Nye, Alejandro Suárez-Bonnet, Simon L Priestnall, James I MacRae, Santiago Zelenay, Kiran Raosaheb Patil, Kevin Litchfield, James C Lee, Tine Jess, Romina S Goldszmid, Caetano Reis e Sousa
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.


Crick (Grant ID: CC2090, Grant title: Reis e Sousa CC2090) Crick (Grant ID: CC2219, Grant title: Lee CC2219) Crick (Grant ID: CC1107, Grant title: STP Bioinformatics & Biostatistics) Crick (Grant ID: CC1067, Grant title: STP Metabolomics) Crick (Grant ID: CC1061, Grant title: STP Experimental Histopathology) Crick (Grant ID: CC2016, Grant title: Stockinger CC2016) Wellcome Trust (Grant ID: 106973/Z/15/Z, Grant title: WT 106973/Z/15/Z)