Circulation of gut pre-activated naïve CD8+ T cells enhances anti-tumor immunity in B cell defective mice

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 tail deletion (µMT), have elevated anti-tumor immunity under specific-pathogen-free condition, depending on CD8+ T cells. Further studies suggest that microbiota-dependent upregulation of type-I IFN inducible genes, including Sca-1, in CD8+ T cells underlies the strong anti-tumor response of BCD mice. Of the CD8+ T cell subpopulations, the most significant difference in Sca-1 expression between wild-type (WT) and BCD mice was seen in naïve CD8+ T cells (CD44lowCD62Lhigh) in peripheral lymphoid and spleen. To further explore whether the upregulation of Sca-1 expression in peripheral CD8+ T cells of BCD mice associates with a unique gene profile, transcriptomic analysis was performed in peripheral CD8+ T cell populations in WT and µMT mice at the single cell level, providing the evidence that among peripheral CD8+ T cells, naïve CD8+ T cells are the most distinct subpopulation between WT and BCD mice. Overall design: Peripheral CD8+ T cell populations derived from WT and B cell defective (µMT) strains each were labeled with oligo DNA-tagged antibodies against CD44 and CD62L (TotalSeq-A provided from BioLegend) and used for the single cell transcriptome analysis.