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Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted by metastasis

ABSTRACT: Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted by metastasis

PROVIDER: PRJNA877282 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR21463845_1.fastq.gz	Fastqsanger.gz
	SRR21463845_2.fastq.gz	Fastqsanger.gz
	SRR21463846_1.fastq.gz	Fastqsanger.gz
	SRR21463846_2.fastq.gz	Fastqsanger.gz

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Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted by metastasis

Project description:CD8+ T cell responses are critical for anti-tumor immunity. While extensively profiled in the tumor microenvironment (TME), recent studies in mice identified responses in lymph nodes (LN) as essential; however, the role of LN in human cancer patients remains unknown. Here, we examined CD8+ T cells in human head and neck squamous cell carcinomas (HNSCC) and regional lymph node (LN) using single-cell genomics. We identified progenitor exhausted CD8+ T cells (TCF7 Exhausted) that were clonally related to terminally exhausted CD8 T cells in the TME. Our results identify an important role for the LN as a reservoir of more functional CD8+ T cells for anti-tumor immune responses in humans.

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Resident memory T cells in regional lymph nodes sustain immunity to cancer

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scRNAseq of stromal cells isolated from mesenteric lymph nodes (MLN), peripheral lymph nodes (PLN) and mandibular lymph nodes (mandLN)

Project description:scRNAseq of stromal cells isolated from mesenteric lymph nodes (MLN), peripheral lymph nodes (PLN) and mandibular lymph nodes (mandLN)

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Dynamic CD8<sup>+</sup> T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes.

Project description:CD8+ T cell responses are critical for anti-tumor immunity. While extensively profiled in the tumor microenvironment, recent studies in mice identified responses in lymph nodes (LNs) as essential; however, the role of LNs in human cancer patients remains unknown. We examined CD8+ T cells in human head and neck squamous cell carcinomas, regional LNs, and blood using mass cytometry, single-cell genomics, and multiplexed ion beam imaging. We identified progenitor exhausted CD8+ T cells (Tpex) that were abundant in uninvolved LN and clonally related to terminally exhausted cells in the tumor. After anti-PD-L1 immunotherapy, Tpex in uninvolved LNs reduced in frequency but localized near dendritic cells and proliferating intermediate-exhausted CD8+ T cells (Tex-int), consistent with activation and differentiation. LN responses coincided with increased circulating Tex-int. In metastatic LNs, these response hallmarks were impaired, with immunosuppressive cellular niches. Our results identify important roles for LNs in anti-tumor immune responses in humans.

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Gene expression signatures for murine B cells from tumor-draining lymph nodes

Project description:To determine the influence of primary tumors on pre-metastatic lymph nodes, we have employed whole genome microarray expression profiling as a discovery platform to identify gene signatures of B cells from tumor-draining lymph nodes, compared with normal lymph nodes. We subcutaneously inoculated C57BL/6 mice with the 4T1 mammary carcinoma. Two weeks later, tumor-draining lymph nodes were dissociated and B cells (CD19+) were sorted. Lymph nodes B cells from normal mice without tumor bearing were set as controls.

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