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Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients.

ABSTRACT: Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients.

PROVIDER: PRJNA475305 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7284620_1.fastq.gz	Fastqsanger.gz
	SRR7284620_2.fastq.gz	Fastqsanger.gz
	SRR7284630_1.fastq.gz	Fastqsanger.gz
	SRR7284630_2.fastq.gz	Fastqsanger.gz
	SRR7284650_1.fastq.gz	Fastqsanger.gz

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Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients

Project description:Tumor-draining lymph node (TDLN) invasion by metastatic cells in breast cancer correlates with poor prognosis and is associated with local immunosuppression, which can be partly mediated by regulatory T cells (Tregs). Here, we study Tregs from matched tumor-invaded and non-invaded TDLNs, and breast tumors. We observe that Treg frequencies increase with nodal invasion, that Tregs express higher levels of co-inhibitory/stimulatory receptors than effector cells. Also, while Tregs show conserved suppressive function in TDLN and tumor, conventional T cells (Tconvs) in TDLNs proliferate and produce Th1-inflammatory cytokines, but are dysfunctional in the tumor. We describe a common transcriptomic signature shared by Tregs from tumors and nodes, including CD80, which is significantly associated with poor patient survival. TCR RNA-sequencing analysis indicates trafficking between TDLNs and tumors and ongoing Tconv/Treg conversion. Overall, TDLN Tregs are functional and express a distinct pattern of druggable co-receptors, highlighting their potential as targets for cancer immunotherapy.

2020-05-26 | E-MTAB-9112 | biostudies-arrayexpress

Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients.

Project description:Tumor-draining lymph node (TDLN) invasion by metastatic cells in breast cancer correlates with poor prognosis and is associated with local immunosuppression, which can be partly mediated by regulatory T cells (Tregs). Here, we study Tregs from matched tumor-invaded and non-invaded TDLNs, and breast tumors. We observe that Treg frequencies increase with nodal invasion, and express higher levels of co-inhibitory/stimulatory receptors than effector cells. Also, while Tregs show conserved suppressive function in TDLN and tumor, conventional T cells (Tconvs) in TDLNs proliferate and produce Th1-inflammatory cytokines, but are dysfunctional in the tumor. We describe a common transcriptomic signature shared by Tregs from tumors and nodes, including CD80, which is significantly associated with poor patient survival. TCR RNA-sequencing analysis indicates trafficking between TDLNs and tumors and ongoing Tconv/Treg conversion. Overall, TDLN Tregs are functional and express a distinct pattern of druggable co-receptors, highlighting their potential as targets for cancer immunotherapy.

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Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients

Project description:Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients

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Gene expression signatures for murine stromal 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 stromal 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 stromal cells (CD45-) were sorted. Lymph nodes stromal cells from normal mice without tumor bearing were set as controls.

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