Fig. 6: Carboplatin induces a pro-inflammatory immune response, effectively priming the TME to facilitate LeY-specific CAR T cell infiltration in PDX-287R.
a Representative images of residual PDX tumors 3 weeks post a single dose of carboplatin treatment (50 mg/kg; n = 12 grafts) or vehicle (n = 7 grafts) using immunohistochemistry for the human epithelial cell marker CK8/18 (scale bars = 50 µm). Cellular composition (%) of human epithelium and murine stroma in each treatment group, as determined by scRNAseq, is also shown. b Proportions of infiltrative cell types within carboplatin-treated (n = 5 samples) and vehicle control (n = 1 sample) stromal tissue (%). c UMAP-defined stromal cell populations. d Violin plots showing GSEA score enriched proportions of M1 and M2 macrophages within carboplatin-treated (n = 245 cells) and vehicle control tissue (n = 135 cells). GSEA statistical and empirical evaluation were used to yield a normalized enrichment score (NES; significance level of 5%), and significance was determined by Welch’s T-test. e Defined macrophage populations isolated from harvested PDX tissue post-carboplatin or control treatment, and their relative expression of M1 phenotypic markers. f Quantification and relative proportion of macrophage upregulation of Ccl5 and Cxcl10 genetic elements encoding chemoattractants within carboplatin-treated (n = 245 cells) and vehicle control tissue (n = 135 cells). g UMAP characterizing distinct populations of CAFs present in harvested tissue. h Dot plots showing normalized gene expression of ECM-associated constituents, immunosuppressive agents and chemotactic factors by cancer-associated fibroblasts (CAFs). i Violin plots showing the proportion of carboplatin-treated (n = 19 cells) or control-treated (n = 73 cells) endothelial cell markers associated with the tumor-associated high endothelial venule (TA-HEV) cellular profile responsible for regulation of lymphocyte trafficking. Significance was determined by GSEA statistical and empirical evaluation to yield a normalized enrichment score (NES; significance level of 5%). Box plots in d, f, and I show the first to third quartile with median, whiskers show the minimum and maximum. Source data are provided as a Source Data file.
