Vitamin D regulates microbiome-dependent cancer immunity

• 成果类型: Article
• 署名作者: Giampazolias, Evangelos; Pereira da Costa, Mariana; Lam, Khiem C.; Lim, Kok Haw Jonathan; Cardoso, Ana; Piot, Cecile; Chakravarty, Probir; Blasche, Sonja; Patel, Swara; Biram, Adi; Castro-Dopico, Tomas; Buck, Michael D.; Rodrigues, Richard R.; Poulsen, Gry Juul; Palma-Duran, Susana A.; Rogers, Neil C.; Koufaki, Maria A.; Minutti, Carlos M.; Wang, Pengbo; Vdovin, Alexander; Frederico, Bruno; Childs, Eleanor; Lee, Sonia; Simpson, Ben; Iseppon, Andrea; Omenetti, Sara; Kelly, Gavin; Goldstone, Robert; Nye, Emma; Suarez-Bonnet, Alejandro; Priestnall, Simon L.; Macrae, James I.; Zelenay, Santiago; Patil, Kiran Raosaheb; Litchfield, Kevin; Lee, James C.; Jess, Tine; Goldszmid, Romina S.; Sousa, Caetano
• 署名单位: Francis Crick Institute; Cancer Research UK; University of Manchester; National Institutes of Health (NIH) - USA; NIH Center for Cancer Research (CCR); NIH National Cancer Institute (NCI); Imperial College London; Francis Crick Institute; University of Cambridge; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Aalborg University; Francis Crick Institute; University of Manchester; Cancer Research UK; University of London; University College London; Francis Crick Institute; Francis Crick Institute; University of London; University of London Royal Veterinary College; Francis Crick Institute; University of London; University College London; UCL Medical School; Royal Free London NHS Foundation Trust; Christie NHS Foundation Trust; Fundacao Champalimaud
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-14034
• DOI: 10.1126/science.adh7954
• 发表日期: 2024-04-26
• 页码: 428-437
• 关键词: d-binding-protein; colorectal-cancer; d-receptor; d supplementation; free survival; d pathway; RISK; association; mechanisms; tumor

摘要

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.