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Immune suppressive landscape in a human esophageal squamous cell carcinoma microenvironment

ABSTRACT: Immune suppressive landscape in a human esophageal squamous cell carcinoma microenvironment

PROVIDER: PRJNA606979 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR11094243_1.fastq.gz	Fastqsanger.gz
	SRR11094243_2.fastq.gz	Fastqsanger.gz
	SRR11094246_1.fastq.gz	Fastqsanger.gz
	SRR11094246_2.fastq.gz	Fastqsanger.gz

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Immune suppressive landscape in a human esophageal squamous cell carcinoma microenvironment

Project description:Properly applying current immunotherapies or developing novel therapeutic strategies relies on a comprehensive understanding of the immune elements of the tumor microenvironment (TME). In this study, we aim to map at single-cell resolution the immune landscape of esophagus squamous cell carcinoma (ESCC), a common, aggressive, but understudied cancer of the gastrointestinal tract. We obtained a detailed immune cell atlas of the ESCC-associated transcriptome from a total of 80,787 tumor-infiltrating immune cells. Significant intertumoral heterogeneity was found among individual ESSC tumors. Exhausted T cells, exhausted NK cells, regulatory T cells, alternatively activated macrophages, and tolerogenic dendritic cells were discovered as the dominant portions of the immune cells in the TME. Dysfunctional T cells were the major proliferative cell compartment among tumor-infiltrating immune cells. In addition, strong potential interactions of immune cells in tumors may contribute to the immunosuppressive status and the progress of tumor development; a six-gene signature, comprising IFNGR1, IFNGR2, IDO1, IL10, CD163, and CD274, were associated with ESCC survival. Our results provided a comprehensive characterization of tumor-infiltrating immune cells in ESCC, indicating that immunosuppression of various kinds was synchronously responsible for the failure of immunosurveillance in ESCC. Specifically targeting the immunosuppressive pathways could reverse the immune-suppressive status and reactivate anti-tumor immune responses in ESCC.

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Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment.

Project description:Cancer immunotherapy has revolutionized cancer treatment, and it relies heavily on the comprehensive understanding of the immune landscape of the tumor microenvironment (TME). Here, we obtain a detailed immune cell atlas of esophageal squamous cell carcinoma (ESCC) at single-cell resolution. Exhausted T and NK cells, regulatory T cells (Tregs), alternatively activated macrophages and tolerogenic dendritic cells are dominant in the TME. Transcriptional profiling coupled with T cell receptor (TCR) sequencing reveal lineage connections in T cell populations. CD8 T cells show continuous progression from pre-exhausted to exhausted T cells. While exhausted CD4, CD8 T and NK cells are major proliferative cell components in the TME, the crosstalk between macrophages and Tregs contributes to potential immunosuppression in the TME. Our results indicate several immunosuppressive mechanisms that may be simultaneously responsible for the failure of immuno-surveillance. Specific targeting of these immunosuppressive pathways may reactivate anti-tumor immune responses in ESCC.

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Project description:Profiles of esophageal squamous cell carcinoma and normal esophageal normal epithelium normal cell line. Analysis provides validation of novel microRNA targets prediction algorithms. esophageal squamous cell carcinoma:14, normal epithelium cell:2

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