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PD-1-stimulated T cell subsets are transcriptionally and functionally distinct

ABSTRACT: PD-1-stimulated T cell subsets are transcriptionally and functionally distinct

PROVIDER: PRJNA731922 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14615907_1.fastq.gz	Fastqsanger.gz
	SRR14615907_2.fastq.gz	Fastqsanger.gz
	SRR14615908_1.fastq.gz	Fastqsanger.gz
	SRR14615908_2.fastq.gz	Fastqsanger.gz
	SRR14615909_1.fastq.gz	Fastqsanger.gz

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PD-1-stimulated T cell subsets are transcriptionally and functionally distinct

Project description:Analysis of 3 subsets of primary human CD4+ T cells (naive, CM, EM) stimulated with anti-CD3, anti-CD28 and PD-L1/PD-L2 for 18 hours. we show that naive, EM, and CM T cell subsets had distinct gene expression profiles following PD-1 ligation.

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PD-1-stimulated T cell subsets are transcriptionally and functionally distinct.

Project description:Despite the obvious inhibitory outcome of PD-1 signaling, an additional series of functions are activated. We have observed that T cells stimulated through the T cell receptor (TCR) and PD-1 primarily do not proliferate; however, there is a population of cells that proliferates more than through TCR stimulation alone. In this study, we performed flow cytometry and RNA sequencing on individual populations of T cells and discovered that unlike naive T cells, which were inhibited following PD-1 ligation, T cells that proliferated more following PD-1 ligation were associated with effector and central memory phenotypes. We showed that these populations had different gene expression profiles following PD-1 ligation with PD-L1 compared to PD-L2. The presence of transcriptionally and functionally distinct T cell populations responsive to PD-1 ligation provides new insights into the biology of PD-1 and suggest the use of T cell subset-specific approaches to improve the clinical outcome of PD-1 blockade.

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A transcriptionally und functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small cell lung cancer treated with PD-1 blockade

Project description:Evidence from mouse chronic viral infection models suggests that CD8+ T cell subsets characterized by distinct expression levels of the receptor PD-1 diverge in their state of exhaustion and potential for reinvigoration by PD-1 blockade. However, it remains unknown whether T cells in human cancer adopt a similar spectrum of exhausted states based on PD-1 expression levels. We compared transcriptional, metabolic, and functional signatures of intratumoral CD8+ T lymphocyte populations with high (PD-1T), intermediate (PD-1N) and no PD-1 expression (PD-1-) from non-small cell lung cancer patients. We observed that, PD-1T T cells show a markedly different transcriptional and metabolic profile as compared to PD-1N and PD-1- lymphocytes, as well as an intrinsically high capacity for tumor recognition. Furthermore, while PD-1T lymphocytes are impaired in classical effector cytokine production, they produce CXCL13 that mediates immune cell recruitment to tertiary lymphoid structures. Strikingly, the presence of PD-1T cells was strongly predictive for both response and survival in a small cohort of non-small cell lung cancer patients treated with PD-1 blockade. The characterization of a distinct state of tumor-reactive, PD-1 bright lymphocytes in human cancer, which only partially resembles that seen in chronic infection, provides novel potential avenues for therapeutic intervention.

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