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Systematic lineage tracing reveals clonal progenitors and long-term persistence of1 tumor-specific T cells during immune checkpoint blockade

ABSTRACT: Systematic lineage tracing reveals clonal progenitors and long-term persistence of1 tumor-specific T cells during immune checkpoint blockade

PROVIDER: PRJNA773805 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16541726_1.fastq.gz	Fastqsanger.gz
	SRR16541726_2.fastq.gz	Fastqsanger.gz
	SRR16541727_1.fastq.gz	Fastqsanger.gz
	SRR16541727_2.fastq.gz	Fastqsanger.gz
	SRR16541728_1.fastq.gz	Fastqsanger.gz

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Systematic lineage tracing reveals clonal progenitors and long-term persistence of tumor-specific T cells during immune checkpoint blockade

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Project description:Paired single-cell RNA and T cell receptor sequencing (scRNA/TCR-seq) has allowed for enhanced resolution of clonal T cell dynamics in cancer. Here, we report scRNA/TCR-seq analysis of 187,650 T cells from 31 tissue regions, including tumor, adjacent normal tissues, and lymph nodes (LN), from 3 patients with lung cancer after immune checkpoint blockade (ICB). Regions with viable cancer cells were enriched for exhausted CD8+ T cells, regulatory CD4+ T cells (Treg), and follicular helper CD4+ T cells (TFH). Tracking T cell clonotypes across tissues, combined with neoantigen specificity assays, revealed that TFH and tumor-specific exhausted CD8+ T cells could be clonally linked to TCF7+ SELL+ progenitors in tumor draining LNs, and progressive exhaustion trajectories of CD8+ T, Treg, and TFH cells with proximity to the tumor microenvironment. Finally, longitudinal tracking of tumor-specific CD8+ and CD4+ T cell clones revealed persistence in the peripheral blood for years after ICB therapy.

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Project description:Paired single-cell RNA and T cell receptor sequencing (scRNA/TCR-seq) has allowed for enhanced resolution of clonal T cell dynamics in cancer. Here, we report a scRNA/TCR-seq analysis of 187,650 T cells from 31 tissue regions, including tumor, adjacent normal tissues, and lymph nodes (LN), from three patients with non-small cell lung cancer after immune checkpoint blockade (ICB). Regions with viable cancer cells are enriched for exhausted CD8+ T cells, regulatory CD4+ T cells (Treg), and follicular helper CD4+ T cells (TFH). Tracking T cell clonotypes across tissues, combined with neoantigen specificity assays, reveals that TFH and tumor-specific exhausted CD8+ T cells are clonally linked to TCF7+SELL+ progenitors in tumor draining LNs, and progressive exhaustion trajectories of CD8+ T, Treg, and TFH cells with proximity to the tumor microenvironment. Finally, longitudinal tracking of tumor-specific CD8+ and CD4+ T cell clones reveals persistence in the peripheral blood for years after ICB therapy.

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