文章：

维生素D调控依赖微生物组的癌症免疫

Vitamin D regulates microbiome-dependent cancer immunity

原文发布日期：2024-04-25

DOI: 10.1126/science.adh7954

类型: Research Article

开放获取: 否

文章简介：

Editor’s summary

The gut microbiome has been shown to modulate the response of cancer patients to therapy, but precisely how microbiota affect anticancer immunity is still being elucidated. Giampazolias et al. report that vitamin D bioavailability in mice influences the composition of the gut microbiome (see the Perspective by Franco and McCoy). After dietary manipulation, vitamin D levels were observed to affect gut bacteria, which in turn improved cancer immunotherapy and antitumor immunity. In humans, low vitamin D levels were correlated with tumor development, and gene signatures of vitamin D activity were associated with improved patient responses to immunotherapy. These findings highlight the connection between vitamin D and the immune system through gut bacteria and may have applications for improving cancer therapies. —Priscilla N. Kelly

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.

简介翻译： 

编辑摘要

肠道微生物组已被证明能调节癌症患者对治疗的反应，但微生物群如何精确影响抗癌免疫力仍在阐明中。Giampazolias 等人报告说，小鼠中维生素 D 的生物利用度影响肠道微生物组的组成（参见 Franco 和 McCoy 的视角文章）。经过饮食操控后，观察到维生素 D 水平影响肠道细菌，这反过来改善了癌症免疫疗法和抗肿瘤免疫力。在人类中，低维生素 D 水平与肿瘤发展相关，而维生素 D 活性的基因特征与患者对免疫疗法的改善反应相关。这些发现突出了维生素 D 通过肠道细菌与免疫系统之间的联系，并可能应用于改善癌症疗法。—Priscilla N. Kelly

摘要

维生素 D 在免疫调节和癌症中的作用已被提出。在这项工作中，我们报告说，维生素 D 可用性增加的小鼠显示出对可移植癌症的更大免疫依赖性抵抗，以及对检查点阻断免疫疗法的增强反应。类似地，在人类中，维生素 D 诱导的基因与对免疫检查点抑制剂治疗的改善反应，以及与癌症免疫力和增加的总生存期相关。在小鼠中，这种抵抗归因于维生素 D 对肠上皮细胞的活性，这改变了微生物组组成，有利于脆弱拟杆菌，后者正向调节癌症免疫力。我们的发现表明维生素 D、微生物共生群落和癌症免疫反应之间先前未被重视的联系。总之，它们突出了维生素 D 水平作为癌症免疫力和免疫疗法成功的一个潜在决定因素。

原文链接：

Vitamin D regulates microbiome-dependent cancer immunity