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CD161 expression of TRM cells counteracts the HPV-associated clinical benefit in oropharyngeal cancer immunotherapy

ABSTRACT: CD161 expression of TRM cells counteracts the HPV-associated clinical benefit in oropharyngeal cancer immunotherapy

PROVIDER: PRJNA940826 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23803176.fastq.gz	Fastqsanger.gz
	SRR23803177.fastq.gz	Fastqsanger.gz
	SRR23803178.fastq.gz	Fastqsanger.gz
	SRR23803179.fastq.gz	Fastqsanger.gz
	SRR23803180.fastq.gz	Fastqsanger.gz

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Similar Datasets

CD161 expression of TRM cells counteracts the HPV-associated clinical benefit in oropharyngeal cancer immunotherapy

Project description:Oropharyngeal squamous cell carcinoma (OPSCC), a distinct head and neck cancer subtype that develops in the oropharynx, is well known to be categorized into human papillomavirus induced (HPV+) and non-HPV induced (HPV-). While HPV+ OPSCC is reported to be clinically advantageous compared to HPV- OPSCC, the heterogeneous responses in HPV+ OPSCC during immunotherapy treatment have not been well characterized at the molecular level. In this study, we assess both tumor and immune cells of the OPSCC tumor microenvironment (TME) via single-cell RNA sequencing (scRNA-seq) and single-cell TCR sequencing (scTCR-seq). By dissecting the transcriptome of OPSCC tumor cells, we find that cancer cell transcriptional diversity may be a strong factor in negating HPV associated clinical benefits. By assessing immune cells, we observed molecular antiviral and anti-tumor characteristics of T cells that is associated with HPV infection, and key cell-cell interaction differences among resident memory T cells (Trm), follicular helper T cells, and B cells. Importantly, we identify a novel molecular state within the HPV+ OPSCC that is distinguished by the expression KLRB1 (CD161) in the Trm that inhibits anti-tumor activity, which may further explain the heterogeneous clinical benefits of HPV+OPSCC. Association of KLRB1 expression of Trm and immunotherapy outcome was confirmed via immunofluorescence analysis, suggesting CD161 as a novel therapeutic target to improve cancer treatment of HPV+ OPSCC.

2024-06-01 | GSE226620 | GEO

Expression data from human cord blood CD161++/CD161+/CD161- CD8+ T cell subsets

Project description:We used microarray to compare gene expression between CD161++/CD161+/CD161-CD8+ T cells from human cord blood.

2012-01-25 | GSE33424 | GEO

Expression data from human cord blood CD161++/CD161+/CD161- CD8+ T cell subsets

Project description:We used microarray to compare gene expression between CD161++/CD161+/CD161-CD8+ T cells from human cord blood. Lymphocytes from freshly obtained human cord blood samples were isolated by Ficoll density centrifugation. CD8+ T cells were purified by negative selection using magnetic beads and subsequently labelled with fluorescent antibodies prior to sorting using MoFlo MLS cell sorter (Dako).

2012-01-25 | E-GEOD-33424 | biostudies-arrayexpress

Expression data from healthy human CD161++CD8aa and CD161++CD8ab T cells

Project description:We used microarrays to compare gene expression between healthy human CD161++CD8aa and CD161++CD8ab T cells.

2012-01-25 | GSE33374 | GEO

Single cell analysis reveals multiple subsets of CD8+ TRM and non-TRM cells with a type 17 signature in the inflamed psoriatic arthritis joint

Project description:CD69+CD103+ tissue-resident memory T-cells (TRM) are increasingly recognised as important drivers of inflammation. To decipher their potential role in inflammatory arthritis, we applied single cell, high-dimensional profiling (CyTOF and scRNAseq) to T-cells isolated from the joint of patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA). We identified three broad groups of synovial CD8+ TRM cells: cytotoxic and Treg-like TRM cells were present in the inflamed joints of patients with both PsA and RA, while CD161+CXCR6+ type 17-like TRM cells with a pro-inflammatory cytokine profile (IL-17A+TNFa+IFNg+) and a distinct transcriptomic signature and a polyclonal, but distinct TCR repertoire, were specifically enriched in the inflamed joints of patients with PsA. Type 17-like cells were also enriched in non-TRM CD8+ T-cells in PsA compared to RA. These findings add substantively to the accumulating evidence that the immunopathology of PsA and RA is different, with a particular role for type 17 cells in PsA.

2023-05-17 | GSE216914 | GEO

Targeting of the CD161 Inhibitory Receptor Enhances T cell-mediated Immunity Against Hematological Malignancies

Project description:The CD161 inhibitory receptor is highly upregulated by tumor-infiltrating T cells in a number of human solid tumor types, and its ligand CLEC2D is expressed by both tumor cells and infiltrating myeloid cells. Here we assessed the role of the CD161 receptor in hematological malignancies. Systematic analysis of CLEC2D expression using the Cancer Cell Line Encyclopedia (CCLE) revealed that CLEC2D mRNA was most abundant in hematological malignancies, including B cell and T cell lymphomas as well as lymphocytic and myelogenous leukemias. CLEC2D protein was detected by flow cytometry on a panel of cell lines representing a diverse set of hematological malignancies. We therefore used yeast display to generate a panel of high-affinity, fully human CD161 monoclonal antibodies (mAbs) that blocked CLEC2D binding. These mAbs were specific for CD161 and had a similar affinity for human and non-human primate CD161, a property relevant for clinical translation. A high-affinity CD161 mAb enhanced key aspects of T cell function, including cytotoxicity, cytokine production and proliferation, against cell lines originating from patients with AML, DLBCL and Burkitt lymphoma. In humanized mouse models, this CD161 mAb enhanced T cell-mediated immunity resulting in a significant survival benefit. ScRNA-seq data demonstrated that CD161 mAb treatment enhanced expression of cytotoxicity genes by CD4 T cells as well as a tissue-resident memory program by CD4 and CD8 T cells that is associated with favorable survival outcomes in multiple human cancer types. These fully human monoclonal antibodies thus represent potential immunotherapy agents for hematological malignancies.

2024-01-02 | GSE220200 | GEO

Expression data from healthy human CD161++CD8aa and CD161++CD8ab T cells

Project description:We used microarrays to compare gene expression between healthy human CD161++CD8aa and CD161++CD8ab T cells. We sorted freshly obtained peripheral blood mononucleocytes from healthy controls by first using magnetic beads to negatively select for CD8a+ T cells, fluorescently labelling isolated cells with antibodies and subsequent sorting using MoFlow MLS cell sorter (DAKO). Sorted samples were snap frozen. RNA was later extracted from the sorted populations prior to hybridization to Affymetrix arrays.

2012-01-25 | E-GEOD-33374 | biostudies-arrayexpress

Gene expression profile of TCR Vdelta1 positive gammadelta T cells expressed CD161

Project description:To elucidate the difference between CD161-negative TCR Vdelta1 and CD161-positive TCR Vdelta1 cells, we performed GeneChip analysis of these two types of cells in peripheral blood mononuclear cells from healthy donors. Such analysis identified 192 genes that were expressed at two-fold or higher levels on CD161-positive TCR Vdelta1 cells than on CD161-negative TCR Vdelta1 cells. Expression of three genes (CCL3, CCL4 and CD161) from this signature was quantified in the same RNA samples by real-time PCR.

2014-01-09 | GSE43402 | GEO

Gene expression profile of TCR Vdelta1 positive gammadelta T cells expressed CD161

2014-01-09 | E-GEOD-43402 | biostudies-arrayexpress

CD161 defines a distinct subset of pro-inflammatory NK cells that are present in the inflamed gut

Project description:CD161 is a C-type lectin like receptor expressed on the majority of Natural Killer (NK) cells, however, the significance of CD161 expression on NK cells has not been comprehensively investigated. We used microarrays to compare gene expression between healthy human CD161+ and CD161- NK cells.

2017-05-10 | GSE98702 | GEO

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