Fig. 5: Descartes-08 generates unique transcriptional profiles that correlate with clinical response.
Transcriptomic analysis of peripheral blood using bulk sequencing (placebo, n = 6; DC-08, n = 14; responder, n = 9; non-responder, n = 5) and scRNA-seq (placebo, n = 7; DC-08, n = 7; responder, n = 5; non-responder, n = 2). a, UMAPs of integrated samples from all analyzed patients in placebo and DC-08 cohorts at SCR and month 3 timepoints showing minimal visual change between cell subsets across timepoints or treatment groups. b–d, Relative percent change from SCR to month 3 in plasmablast (b), pDC (c) and Treg (d) composition. Box-and-whisker plots show the median, interquartile range and full range of data, along with individual data points. e, Bulk RNA-seq GSEA of hallmark gene sets. f–h, scRNA-seq GSEA of hallmark gene sets in plasmablasts (f), pDCs (g) and Treg (h) cells showing enrichment of pro-immune gene sets in patients treated with DC-08 relative to placebo and in responders compared to non-responders. i–n, scRNA-seq GSEA of B cell subsets (B cells (i), naive B cells (j), intermediate B cells (k) and memory B cells (l)) and T cells (CD8+ T cells (m) and CD4+ T cells (n)). Asterisks (*) in heatmaps indicate statistical significance at P values indicated in the inset. Genes were considered differentially expressed at an FDR < 0.1 (Benjamini–Hochberg correction for multiple comparisons) and an absolute log2(fold change) > 0.585 (1.5-fold change). Further details on statistical analyses are provided in Methods. Source data for b–d are provided for this figure. HSPC, hematopoietic stem and progenitor cell; ILC, innate lymphoid cell; ASDC, AXL+SIGLEC-6+ dendritic cell; cDC1, conventional type 1 dendritic cell; cDC2, conventional type 1 dendritic cell; CTL, cytotoxic T lymphocyte; DN, down; dnT, double-negative T cell; Eryth, erythrocyte; gdT, gamma-delta T cell; MAIT, mucosal-associated invariant T; Mono, monocyte; NES, normalized enrichment score; UP, up; UV, ultraviolet.
