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Table 2 Metabolic analysis of T cells and CAR-T cells based on single-cell techniques

From: Rewiring mitochondrial metabolism to counteract exhaustion of CAR-T cells

Type Method Cell types Cell source Main conclusion References
Single-cell RNA-seq 10X Genomics CAR-T cells 5 healthy donors 41BB CAR-T cells had increased markers associated with CD8 central memory T cells and favored fatty acid metabolism [141]
1. Bulk-seq
2. 10X Genomics
CAR-T cells 24 patients with LBCL, 137,326 residual cells Heterogeneity of CAR T cell infusion products contributes to variation in efficacy and toxicity after axi-cel therapy [171]
scTCR/transcriptome by 10X Genomics peripheral blood lymphocytes after TIL infusion 1 patient with metastatic colorectal cancer After ACT, the TILs gene expression patterns changed, but IL7R, ITGB1, KLF2 and ZNF683 remained expressed in the persistent clonotypes, compared to the non-persistent clonotypes [161]
Single-cell Proteome 1. CyTOF
CD8 T cells 1. Tumor tissue (n = 6) and healthy adjacent tissue from the same patients (n = 6)
2. Unrelated healthy donor PBMCs (n = 5) and lymph node biopsies (n = 3)
1. Three check points were identified of metabolic switching of naive human CD8+ T cells
2. Single-cell metabolic regulome profiling(scMEP) metabolic states associated clearly with distinct immunological phenotypes
Mass Cytometry CD8 T cells
CAR-T cells
1. Naive or LMV infected WT C57BL/6 mice
2. 2 advanced NHL patients receiving axi-cel therapy
A distinct metabolic state in early-activate T cells (most abundant 5 days post-infection) characterized by maximal expression of glycolytic and oxidative metabolic proteins [150]
Met-Flow Human PBMCs 12 donors, 150,000 cells per leukocyte population 1. Metabolic remodeling occurs during T cell activation
2. T cell memory subsets show differential metabolic phenotypes; The TCM and TEM populations both expressed higher levels of ACAC, PRDX2, and CPT1A, in contrast to naive and TTEMRA subsets
Multiplexed single-cell approaches Ins-seq Monocytes and macrophages 7648 cells from MCA205 tumor-bearing mice 1. Arginase 1-expressing cells within tumor is a metabolic immune signature of suppressive activity
2.A novel group of Arg1 + Trem2 + regulatory myloid(Mreg) cells was found and cellular markers, metabolic activity and associated pathways were defined
1. 10X Genomics
2. Compass
Pathogenic and non-pathogenic Th17 cells C57BL/6 wild-type mice 1. Pathogenic Th17 maintain higher aerobic glycolysis and TCA activity, whereas non-pathogenic Th17 oxidize fatty acids to produce ATP
2. Th17 pathogenicity was associated with arginine and downstream polyamine metabolism with enhanced polyamine-related enzyme expression in pathogenic Th17 and suppressed levels in Treg cells
1. scRNA-seq
2. Mass cytometry
3. scATAC-seq
Human PBMCs 1. Young/Aged healthy adults
2. Young/Aged COVID-19 patients
3. Young/Aged COVID-19 patients recovered
Immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with other immune cells [163]