Vitamin D regulates microbiome-dependent cancer immunity
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Evangelos Giampazolias Mariana Pereira Da Costa Khiem C Lam Jonathan Lim Ana Cardoso Cecile Piot Probir Chakravarty Sonja Blasche Swara Patel Adi Biram Tom Castro Dopico Michael Buck Richard R Rodrigues Gry Juul Poulsen Susana Palma-Duran Neil Rogers Maria A Koufaki Carlos Munoz 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 Priestnall James MacRae Santiago Zelenay Kiran Raosaheb Patil Kevin Litchfield James Lee Tine Jess Romina S Goldszmid Caetano Reis e Sousa
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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.
Journal details
Journal
Science
Volume
384
Issue number
6694
Pages
428-437
Available online
Publication date
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Publisher website (DOI)
10.1126/science.adh7954
Europe PubMed Central
38662827
Pubmed
38662827
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