Fig. 2
CAR-T cell behaviors throughout clinical treatment correlate with therapeutic response. Single-cell sequencing has been applied to interrogate in vivo clonal kinetics and molecular profiles that regulate the fate of CAR-T cells after infusion. a Different CAR-T cell subsets lead to divergent differentiation trajectories after infusion [186, 187]; b A model of in vivo dynamic changes of CAR-T cells post infusion was proposed [192]; c The phenotypes of CAR-T cells were associated with CD19-positive relapse [225] and CD19-negative relapse [189]; d Transcriptional mechanisms of response vary by CAR-T products [224]; e The long-persisting CD4+ CAR-T cells exhibited cytotoxic characteristics along with proliferation, cytokine expression, metabolic activity, and in vitro response to CAR stimulation [191]; f CAR-T cell exhaustion during exposure to prolonged tumor antigen was considered as one of the major causes resulting in tumor progression and immunotherapy failures [41]; g CD2 on T cells was associated with directional migration, and the interaction between CD2 on T cells and CD58 on lymphoma cells accelerated serial killing. LAG3 lymphocyte activation gene-3, TOX thymocyte selection-associated high mobility group box, CAS8 caspase 8, NKG7 natural killer cell protein 7, GNYL Granulysin, GZMB Granzyme B, GZMK Granzyme K, CAR-T chimeric antigen receptor T, Th2 T helper 2, TSCM T memory stem cell, TCM central memory T cell, B-ALL B-cell acute lymphoblastic leukemia, tisa-cel tisagenlecleucel, axi-cel axicabtagene ciloleucel, ICANS immune effector cell-associated neurotoxicity syndrome, Treg regulatory T cell, CR complete response, scATAC-seq single-cell assay for transposase-accessible chromatin using sequencing, NR no response, BLIMP1 B lymphocyte-induced maturation protein 1, NR4A3 nuclear receptor subfamily 4 group A member 3, BATF basic leucine zipper ATF-like transcription factor, IRF4 interferon regulatory factor 4