RNA-sequencing of ex vivo exhausted human antigen-specific T cells

Tumor-specific T cells are frequently exhausted by chronic antigenic stimulation. To explore new pathways for reinvigoration of anti-tumor immune functions, we developed a human ex vivo exhaustion model by repetitive antigenic stimulation of primary CD8 T cells. This results in T cells that resemble patient-derived T cells in tumors on a phenotypic and transcriptional level.

Type: RNASeq
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001009754	Tumor-specific T cells are frequently exhausted by chronic antigenic stimulation. To explore new pathways for reinvigoration of anti-tumor immune functions, we developed a human ex vivo exhaustion model by repetitive antigenic stimulation of primary CD8 T cells. This results in T cells that resemble patient-derived T cells in tumors on a phenotypic and transcriptional level. Four human healhy donor CD8+ T cells were isolated, transduced with an NY-ESO-1 TCR lentivirus construct, stimulated in four different conditions (Trested, Ttumor, Tex, Teff) with T2 tumor cells and specific peptides over 12 days. Cells were then sorted for TCR Vbeta 13.1+ (NY-ESO-1 TCR) CD8+ CD3+ CD56- CD4- DAPI- cells. RNA-seq TruSeq libraries were generated from polyA-enriched mRNA isolated from the samples, and sequenced in paired-end mode (2x51bp) on 2 lanes of an Illumina NovaSeq 6000 flow-cell. FASTQ sequence files were generated with the Illumina RTA version 3.4.4 and Base-calling Version bcl2fastq-2.20.0.422.	Illumina NovaSeq 6000	16

Publications	Citations
Deletion of SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy. Trefny MP, Kirchhammer N, Auf der Maur P, Natoli M, Schmid D, Germann M, Fernandez Rodriguez L, Herzig P, Lötscher J, Akrami M, Stinchcombe JC, Stanczak MA, Zingg A, Buchi M, Roux J, Marone R, Don L, Lardinois D, Wiese M, Jeker LT, Bentires-Alj M, Rossy J, Thommen DS, Griffiths GM, Läubli H, Hess C, Zippelius A. Nat Commun 14: 2023 86	18

Publications

Citations

Deletion of SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy.
Trefny MP, Kirchhammer N, Auf der Maur P, Natoli M, Schmid D, Germann M, Fernandez Rodriguez L, Herzig P, Lötscher J, Akrami M, Stinchcombe JC, Stanczak MA, Zingg A, Buchi M, Roux J, Marone R, Don L, Lardinois D, Wiese M, Jeker LT, Bentires-Alj M, Rossy J, Thommen DS, Griffiths GM, Läubli H, Hess C, Zippelius A. Nat Commun 14: 2023 86