Vitamin D regulates microbiome-dependent cancer immunity

Evangelos Giampazolias, Mariana Pereira da Costa1, 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-Duran1, 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,mEmma 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

Science | 384 | pages 428-437 (2024)

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.