Most of DEPs were downregulated in B-ALL patients and highly enriched in actin binding and actin cytoskeleton organization, among others (Figure 1B,C; Supplemental Figure S3). SEE PDF Given the significant differences in plasma molecular signatures between B-ALL patients and HC, we next performed plasma proteomic and metabolomic analyses of samples collected from the different time points relative to pretreatment samples. Actin cytoskeleton organization was identified in WPC3 (Figure 2A,C,E), suggesting that cytoskeleton organization was disrupted. An elevated plasma TGs level may result from adipose tissue lipolysis under hyperinflammatory condition.4 Free fatty acids and purine metabolites were identified in whole metabolome cluster 2 (WMC2) (Figure 2B; Supplemental Table S10). To further elucidate the dynamics of plasma proteome and metabolome during CS, we made co-expression clustering analyses in CS patients. Since IL-6 is a critical and multifunctional cytokine in CAR-T cell-mediated CS, we identified sets of covarying molecules that were implicated in epithelial mesenchymal transition, glutathione metabolism and tryptophan metabolism in concert with IL-6 (Figure 3A–D), further revealing a potential regulatory crosstalk between tissue remodeling, metabolic reprogramming and IL-6.