Fig. 3: Tumor HSP70+ CD8+ T cells are sensitive to ribosome-targeting therapy.
From: Targeting ribosomes reprograms the tumour microenvironment and augments cancer immunotherapy
a Heatmap showing the cellular ribosome biogenesis and 19 curated CD8+ T cell states across CD8+ T cell clusters. Right single- column heatmap showing the correlation levels between cellular ribosome biogenesis and 19 CD8+ T cell states. b Expression pattern of cellular ribosome biogenesis, CD8+ Tstr state, HSPA1A and HSPA1B along pseudotime in the trajectory of CD8+ T cells. c, d Multicolor-immunostaining of rRNA (Y10B), CD8+ T cells (CD8) and stress response marker (HSP70) in tissues of CRC, LIHC, LUAD (lung adenocarcinoma) and STAD (c). Scale bar for all immunostaining images = 20 µm. ROIs A and B represent HSP70+ CD8+ T (Tstr), C and D represent HSP70- CD8+ T cells, (d) showing the intensity of HSP70 and rRNA levels for each ROI grouped by HSP70+ CD8+ and HSP70- CD8+ T cells. e Dotplot showing expressions of marker genes of each T cell subtype of tumor murine models. Dot size indicates proportion of cells expressing genes, dot color indicates mean expression of genes. f Boxplots showing cellular ribosome biogenesis grouped by HSP70+ CD8+ T cells and HSP70- CD8+ T cells of tumor murine models. g Boxplots showing cellular ribosome biogenesis in HSP70+ CD8+ T cells and HSP70- CD8+ T cells of tumor murine models grouped by ctrl and CX-5461 treatment. h Heatmaps showing tissue prevalence of each T cell subtype estimated by Ro/e score grouped by ctrl and CX-5461 treatment of tumor murine models. i Heatmaps showing marker genes expression of granzymes in HSP70+/HSP70- CD8+ T cells of CX-5461 administrated tumor murine models. j Pseudo immunofluorescence based on Visium HD images of CRC showing the spatial organization of spots assigned to cellular ribosome biogenesis levels, CD8+ T cell stress response state, Tregs (FOXP3) and T cell (CD3D) markers. k Kaplan–Meier plots showing the overall survival for each subgroup of the CD8+ T cell infiltration stratified by ribosome biogenesis levels within BRCA (breast carcinoma), CRC, LIHC, lung cancer, kidney cancer and UCEC (endometrial carcinoma) of the TCGA.
