Dataset Information

10X single-cell RNASeq profiling of human CD8+ T cells from advanced metastatic melanoma tumor samples and paired peripheral blood

ABSTRACT: The ability to monitor anti-tumor CD8+ T cell responses in the blood has tremendous therapeutic potential. However, tracking tumor antigen-specific CD8+ T cells in the blood is challenging due to their small number and limited reagents to track these cells. We asked whether paired single-cell RNA and T cell receptor (TCR) sequencing could be used to detect and characterize “tumor matching” (TM) CD8+ T cells in the blood of advanced melanoma patients using the TCR as a molecular barcode. By leveraging the transcriptome, we characterized these cells, and identified candidate cell surface markers for to enrich this population. These data show that the TCR can be used to identify tumor-relevant cells for characterization, reveal unique transcriptional properties of TM cells, and develop marker panels for tracking and analysis of these cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE159251 | GEO | 2021/01/13

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background Clinical success of T cell receptor (TCR) gene therapy has previously been demonstrated for NY-ESO-1 TCR gene therapy. To increase numbers of cancer patients that can be treated with TCR gene therapy we aimed to identify a novel set of high-affinity cancer specific TCRs targeting different cancer testis (CT) antigens in prevalent HLA class I alleles. Methods In this study, we selected based on publicly available gene expression databases the most promising CT genes to target. From these selected genes we identified by HLA peptidomics the naturally processed and presented HLA class I peptides. With these peptide-HLA tetramers were generated, and by single cell sorting CT specific CD8+ T cells were selected, and expanded from the allo-HLA repertoire of healthy donors. By several functional assays high avidity CT-specific T cell clones with safe recognition pattern were selected. To evaluate the potential for clinical application in TCR gene therapy, TCRs were sequenced and transferred into peripheral blood derived CD8+ T cells. Results In total we identified, 7 novel CT-specific TCRs that effectively target MAGE-A1, MAGE-A3, MAGE-A6 and MAGE-A9 in the context of human leukocyte antigen(HLA) -A1, -A2, -A3, -B7, -B35 and -C7. TCR gene transfer into CD8⁺ T cells resulted in efficient cytokine production and cytotoxicity of variety of different tumor types without detectable cross-reactivity. In addition, major in vivo antitumor effects of MAGE-A1 specific TCR engineered CD8⁺ T cells was observed in an orthotopic xenograft model for established multiple myeloma, in which bone marrow located tumor cells were completely eradicated after T cell injection. Conclusion The identification of 7 novel CT-specific TCRs, reactive against CT antigens presented in a variety of different HLA class I alleles, allows selection of therapeutic TCRs for an increased number of cancer patients, and will improve development of personalized TCR gene therapy.

Dataset Information

10X single-cell RNASeq profiling of human CD8+ T cells from advanced metastatic melanoma tumor samples and paired peripheral blood

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets