Circulation of gut-preactivated naïve CD8 + T cells enhances antitumor immunity in B cell-defective mice
| Autor: | Hiroyuki Sato, Tasuku Honjo, Michio Tomura, Akiko Nishii, Sidonia Fagarasan, Kenji Chamoto, Michio Miyajima, Ryuji Suzuki, Rosemary J. Menzies, Maryam Akrami |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Multidisciplinary T cell Cytidine deaminase Biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Immunity 030220 oncology & carcinogenesis medicine Cancer research Cytotoxic T cell Mesenteric lymph nodes Stem cell CD8 B cell |
| Zdroj: | Proceedings of the National Academy of Sciences. 117:23674-23683 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2010981117 |
| Popis: | 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, naive 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+ naive subset is endowed with enhanced mitochondrial activity and antitumor effector potential. The heterogeneity and functional versatility of the systemic naive 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. |
| Databáze: | OpenAIRE |
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