Fig. 5: Multimodal single-cell profiling reveals that the FGFR4.28HTM.28z-CD276.8HTM.BBz BiCisCAR exhibits the highest cytotoxicity activity. | Nature Communications

Fig. 5: Multimodal single-cell profiling reveals that the FGFR4.28HTM.28z-CD276.8HTM.BBz BiCisCAR exhibits the highest cytotoxicity activity.

From: CAR T-cells targeting FGFR4 and CD276 simultaneously show potent antitumor effect against childhood rhabdomyosarcoma

Fig. 5

A Workflow of CITE-Seq for simultaneous protein and transcript analysis of tumor-infiltrating CAR T-cells at day 11 post-infusion using a JR IM orthotopic model (created with BioRender.com). ADT, antibody-derived tag; HTO, hashtag oligonucleotide. B WNN UMAP visualization of tumor-infiltrating T-cells from mice treated using five CAR T-cells with biological replicates. Each dot represents a single cell and cell clusters are labeled by numbers. The black perimeter lines encircle the cell clusters C1, C3, and C7, and the percentages of cells in these clusters are shown. C The percentages (means of 2 biological replicates) of each cell subpopulation from five CAR T-cells treated mice. D Volcano plot of differentially expressed genes (DEGs) between the 28HTM.28z-8HTM.BBz BiCisCAR and 4 other CAR T-cells infiltrating in JR I.M xenografts. Genes with an -Log10 P (adjusted P, two-sided nonparametric Wilcoxon rank-sum test) <20 and │log2 fold change│ > 0.5 are shown in red (n = 18). The top 20 highly expressed genes ranked by average log2 fold change are labeled and associated with T-cell cytotoxicity. E Heatmap of these top 20 genes expressed in CAR T-cells isolated from JR I.M xenograft tumors. The FGFR4.28HTM.28z-CD276.8HTM.BBz BiCisCAR T-cells exhibited the highest expression of T-cell cytotoxicity genes among all CAR T cells. The colored scale bar represents z-score values for gene expression. Source data is provided as a Source Data file.

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