Extended Data Fig. 7: Ligand-receptor regulatory analysis of type 2 CAR T cells.

a, Correlation between Cytotoxic Score and Coinhibitory Score of all the Cluster 2 cells in Fig. 2a. The regression line is indicated, with the 95% confidence area shown in shaded colour. Spearman correlation coefficient and the associated p-value are shown. Genes defining each module are listed. b, Single-cell expression comparisons of Coinhibitory Score and Coinhibitory ADT Score in Cluster 2 cells between persistence groups in the Discovery Cohort. c, Identification of ligand-receptor (L-R) interactions originating from type 2 enriched Cluster 7 cells in Fig. 2c, predominantly interacting with Cluster 1 cells through type 2 L-R pairs. The thickness of edges is proportional to correlation weights, and edge colour corresponds to the Cluster ID. d, Identification of L-R interactions targeting Cluster 1 cells in Fig. 2c, revealing that cells from the majority of other clusters predominantly regulate these cells through type 2 L-R pairs. e, Differentially expressed genes (DEGs) specific to Cluster 1 in comparison to all other clusters in Fig. 2c, along with the expression distribution of the Cytotoxic Score. Genes defining this module include GZMA, GZMB, GZMH, GNLY, PRF1, and NKG7. f, Corresponding signalling pathways regulated by the DEGs identified in Cluster 1. Pathway terms are ranked by –log 10 (p-value). z score is computed and used to reflect the predicted activation level (z > 0, activated/upregulated; z < 0, inhibited/downregulated; z ≥ 2 or z ≤ −2 can be considered significant). g, Heatmap showing the average expression levels of coinhibitory-related genes or ADT proteins across all single cells within each identified cluster in Fig. 2c. The expression of TIM-3 and its encoding gene HAVCR2 is observed to be high in Cluster 1. h, Correlation between Cytotoxic Score and Coinhibitory Score of all the Cluster 1 cells in Fig. 2c. The regression line is indicated, with the 95% confidence area shown in shaded colour. Spearman correlation coefficient and the associated p-value are shown. Genes defining each module are listed in (a). i, Comparison of cell proportion in Cluster 1 between persistence groups in the Validation Cohort. j, Single-cell expression comparisons of Coinhibitory Score and Coinhibitory ADT Score in Cluster 1 cells between persistence groups in the Validation Cohort. Violin plot shows expression distribution of the top 10% single cells from each individual among n = 48 (b) and n = 46 (j) patients or healthy donors. Scatter plot shows mean ± s.e.m. from n = 46 (i) patients or healthy donors. Significance levels were calculated with two-tailed Spearman’s rank correlation test (a, h), two-tailed Mann-Whitney test (b, e, i, and j), or right-tailed Fisher’s Exact Test (f).