Long-term survival and antitumor immunity of adoptively transferred CD8+ T cells is dependent on their metabolic fitness, but approaches to isolate therapeutic T cells based on metabolic features are not well established.
Researchers utilized a lipophilic cationic dye tetramethylrhodamine methyl ester (TMRM) to identify and isolate metabolically robust T cells based on their mitochondrial membrane potential (DJm). Comprehensive metabolomic and gene expression profiling demonstrated global features of improved metabolic fitness in low-DJm-sorted CD8+ T cells.
Transfer of these low-DJm T cells was associated with superior long-term in vivo persistence and an enhanced capacity to eradicate established tumors compared with high-DJm cells. Use of DJm-based sorting to enrich for cells with superior metabolic features was observed in CD8+ , CD4+ T cell subsets, and long-term hematopoietic stem cells.
This metabolism-based approach to cell selection may be broadly applicable to therapies involving the transfer of HSC or lymphocytes for the treatment of viralassociated illnesses and cancer.