GSE175793
Fingerprints of Hepatocellular Carcinoma-Infiltrated  ?dT Cells Revealed by Single-Cell Sequencing
We report the application of single cell RNA sequencing for profiling the fingerprints of ?dT cells of hepatocellular carcinoma compared with healthy donors. By comparing the transcriptome and TCR clonality of ?dT cells from 3 HCC patients and expanded ?dT cells from 3 healthy donors, we found that expanded ?d T cells derived from different donors shared great transcriptomic similarity and we found higher enrichments of major ?d TCRs in expanded ?d T cells compared to infiltrated but not peripheral ones in HCC. Analysis of differentiation trajectory demonstrated a branched structure in expanded ?d T cells, implying functional and differentiation stage diversity, and ?d T cells from HCC patients are localized to the far end of the trajectory. Furthermore, GVSA analyses made on metabolic pathways demonstrated strong enrichments in major metabolic pathways such as OXPHOS, glycolysis, and fatty acid metabolism in expanded ?d T cells versus peripheral ones of HCC. The comparison indicated higher cytotoxicity score of expanded ?d T cells compared to infiltrated or peripheral ones of HCC. The successful application of allogeneic ?d T cells immunotherapy in late-stage liver cancer patients was supported by our current scRNA transcriptomic analyses, which suggested strong anti-tumor functional complementation by the ex-vivo expanded ?d T cells. Overall design: We report the application of single cell RNA sequencing for profiling the fingerprints of ?dT cells of hepatocellular carcinoma compared with healthy donors. Transcriptomic and TCR clonality analysis were both applied. The results showed that expanded ?d T cells derived from different donors shared great transcriptomic similarity and higher enrichments of major ?d TCRs in expanded ?d T cells. Analysis of differentiation trajectory demonstrated a branched structure in expanded ?d T cells, implying functional and differentiation stage diversity, and ?d T cells from HCC patients are localized to the far end of the trajectory. Furthermore, GVSA analyses made on metabolic pathways demonstrated strong enrichments in major metabolic pathways such as OXPHOS, glycolysis, and fatty acid metabolism in expanded ?d T cells versus peripheral ones of HCC. The comparison indicated higher cytotoxicity score of expanded ?d T cells compared to infiltrated or peripheral ones of HCC.