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Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function [scRNA-seq]

ABSTRACT: Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function [scRNA-seq]

PROVIDER: PRJNA928414 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23246855_1.fastq.gz	Fastqsanger.gz
	SRR23246855_2.fastq.gz	Fastqsanger.gz
	SRR23246856_1.fastq.gz	Fastqsanger.gz
	SRR23246856_2.fastq.gz	Fastqsanger.gz
	SRR23246857_1.fastq.gz	Fastqsanger.gz

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Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function [scRNA-seq]

Project description:Gamma delta (γδ) T cells reside within human tissues including tumors, but their role in mediating anti-tumor response with immune checkpoint inhibition is unknown. Using single-cell approaches, we found that kidney cancers are infiltrated by diverse Vδ2- γδ T cells, with equivalent representation of Vδ1+ and Vδ1- cells, that are distinct from γδ T cells found in normal human tissues. These tumor-resident Vδ2- T cells can express the transcriptional program of exhausted alpha beta (ab) CD8+ T cells as well as canonical markers of terminal T cell exhaustion including PD-1, TIGIT and TIM-3. While Vδ2- γδ T cells have blunted IL-2 production, they retain expression of cytolytic effector molecules and costimulatory receptors like 4-1BB. Exhausted Vδ2- γδ T cells are comprised of three distinct populations that lack TCF-7, are clonally expanded, express of cytotoxic molecules, and possess multiple Vδ2- TCRs. Human tumor-derived Vδ2- γδ T cells maintain cytotoxic function and pro-inflammatory cytokine secretion in vitro. The transcriptional program of Vδ2- T cells in pre-treatment tumor biopsies predicted subsequent clinical responses to PD-1 blockade in vivo in cancer patients. Thus, Vδ2- γδ T cells within the tumor microenvironment can contribute to anti-tumor efficacy.

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Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function [bulk RNA-seq]

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Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function

Project description:Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function

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Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function [bulk RNA-seq]

Project description:Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function [bulk RNA-seq]

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Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-01-31 | GSE223809 | GEO

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Project description:γδ T cells provide rapid cellular immunity against pathogens. Here, we conducted matched single-cell RNA-sequencing and γδ-TCR-sequencing to delineate the molecular changes in γδ T cells during a longitudinal study following mRNA SARS-CoV-2 vaccination. While the first dose of vaccine primes Vδ2 T cells, it is the second administration that significantly boosts their immune response. Specifically, the second vaccination uncovers memory features of Vδ2 T cells, shaped by the induction of AP-1 family transcription factors and characterized by a convergent central memory signature, clonal expansion, and an enhanced effector potential. This temporally distinct effector response of Vδ2 T cells was also confirmed in vitro upon stimulation with SARS-CoV-2 spike-peptides. Indeed, the second challenge triggers a significantly higher production of IFNγ by Vδ2 T cells. Collectively, our findings suggest that mRNA SARS-CoV-2 vaccination might benefit from the establishment of long-lasting central memory Vδ2 T cells to confer protection against SARS-CoV-2 infection.

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