| First Author | Akrami M | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 38 | Pages | 23674-23683 |
| PubMed ID | 32907933 | Mgi Jnum | J:296364 |
| Mgi Id | MGI:6459218 | Doi | 10.1073/pnas.2010981117 |
| Citation | Akrami M, et al. (2020) Circulation of gut-preactivated naive CD8(+) T cells enhances antitumor immunity in B cell-defective mice. Proc Natl Acad Sci U S A 117(38):23674-23683 |
| abstractText | 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 micro-membrane targeted deletion (microMT) 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. |
