2020年9月22日
Circulation of gut-preactivated naïve CD8+T cells enhances antitumor immunity in B cell-defective mice
Proceedings of the National Academy of Sciences
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- 巻
- 117
- 号
- 38
- 開始ページ
- 23674
- 終了ページ
- 23683
- 記述言語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1073/pnas.2010981117
- 出版者・発行元
- Proceedings of the National Academy of Sciences
The gut microbiome has garnered attention as an effective target to boost immunity and improve cancer immunotherapy. We found that B cell-defective (BCD) mice, such as µ-membrane targeted deletion (µMT) and activation-induced cytidine deaminase (AID) knockouts (KOs), have elevated antitumor immunity under specific pathogen-free but not germ-free conditions. Microbial dysbiosis in these BCD mice enriched the type I IFN (IFN) signature in mucosal CD8+T cells, resulting in up-regulation of the type I IFN-inducible protein stem cell antigen-1 (Sca-1). Among CD8+T cells, naïve cells predominantly circulate from the gut to the periphery, and those that had migrated from the mesenteric lymph nodes (mLNs) to the periphery had significantly higher expression of Sca-1. The gut-educated Sca-1+naïve subset is endowed with enhanced mitochondrial activity and antitumor effector potential. The heterogeneity and functional versatility of the systemic naïve CD8+T cell compartment was revealed by single-cell analysis and functional assays of CD8+T cell subpopulations. These results indicate one of the potential mechanisms through which microbial dysbiosis regulates antitumor immunity.
- リンク情報
- ID情報
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- DOI : 10.1073/pnas.2010981117
- ISSN : 0027-8424
- eISSN : 1091-6490