Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity [scRNA-seq]

ABSTRACT: Tumor microenvironment (TME) plays critical roles in both tumor progression and immunotherapeutic efficacy. Here using single-cell RNA sequencing (scRNA-seq), we described the TME heterogeneity and found a specific state of CCL22+ dendritic cell (mregDC) cross talk close to regulatory T cells (Treg). We analyzed cell–cell communication mediated by ligand–receptor interactions and finally found that mregDCs probably attract Treg cells via chemotaxis and physically interact with them in tumor. Within this cross talk, Treg cells received activation signals from mregDCs and upregulated suppressive and adhesion molecules, including PD-1, ICOS, CTLA-4 and OX-40, further enhancing their interaction with mregDCs. In turn, the association of Treg cells with mregDCs restrained the trafficking of tumor antigen-bearing dendritic cells to draining mesenteric lymph nodes and thus dampened the presentation of tumor antigens to initiate anti-tumor immune responses in a cell contact dependent manner.

ORGANISM(S): Mus musculus

PROVIDER: GSE234182 | GEO | 2024/07/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A Lactate-induced SREBF2-dependent genetic program drives an immunotolerant dendritic cell population during cancer progression [scATAC-seq]

Project description:Dendritic cells (cDCs) are essential mediators of anti-tumor immunity. Cancers have developed mechanisms to render DCs dysfunctional within the tumor microenvironment. Utilizing CD63 as a unique surface marker, we demonstrate that mature regulatory DCs (mregDCs) suppress DC antigen cross-presentation while driving TH2 and regulatory T cell differentiation within tumor-draining lymph node tissues. Transcriptional and metabolic studies show that mregDC functionality is dependent upon the mevalonate biosynthetic pathway and the master transcription factor, SREBP2. Melanoma-derived lactate activates DC SREBP2 in the tumor microenvironment (TME) and drives mregDC development from conventional DCs. DC-specific genetic silencing and pharmacologic inhibition of SREBP2 promotes anti-tumor CD8+ T cell activation and suppresses melanoma progression. CD63+ mregDCs reside within the sentinel lymph nodes of melanoma patients. Collectively, this work describes a tumor-driven SREBP2-dependent program that promotes CD63+ mregDC development and function while serving as a promising therapeutic target for overcoming immune tolerance in the TME.

2024-05-13 | GSE253589 | GEO

A Lactate-induced SREBF2-dependent genetic program drives an immunotolerant dendritic cell population during cancer progression [Spatial transcriptomics]

2024-05-13 | GSE253588 | GEO

A Lactate-induced SREBF2-dependent genetic program drives an immunotolerant dendritic cell population during cancer progression [CITEseq]

2024-05-13 | GSE253586 | GEO

A Lactate-induced SREBF2-dependent genetic program drives an immunotolerant dendritic cell population during cancer progression [scRNAseq_mouse]

2024-05-13 | GSE253592 | GEO

A Lactate-induced SREBF2-dependent genetic program drives an immunotolerant dendritic cell population during cancer progression [scRNAseq_human]

2024-05-13 | GSE253590 | GEO

Intratumoral mregDC and Tfh-like niches enable local reinvigoration of CD8 T cells following PD-1 blockade

Project description:While T cell accumulation in tumors is associated with response to immune checkpoint blockade (ICB), many T cell-rich tumors fail to respond to ICB. Here we leveraged a large neoadjuvant PD-1 blockade trial in hepatocellular carcinoma (HCC) to search for correlates of ICB response within T cell-rich tumors. Paired scRNAseq/TCRseq of nearly one million immune cells revealed that tumor responses to ICB correlated with significant clonal expansion of intratumoral CH25H+CXCL13+IL-21+CD4 T cells and GranzymeK+PD-1+CD8 effector T cells, whereas terminally exhausted CD39hiToxhiPD-1hi CD8 clones dominated in non-responders. Notably, proliferating and progenitor CD8 T cells clones were found in tumors of responders and non-responders. However, tumors from responders were highly enriched in mregDCs, a DC state triggered by capture of tumor debris, which formed physically interacting cellular triads with Tfh-like CD4 and progenitor-like CD8 T cells. Receptor-ligand analysis revealed unique interactions within these triads that may promote progenitor CD8 T cell differentiation into effector cells upon PD-1 blockade. These results suggest that discrete cellular niches that include mregDCs and Tfh-like CD4 T cells might control the differentiation of tumor-specific progenitor CD8 T cell clones into effective anti-tumor T cells in human tumors.

2023-06-16 | GSE206325 | GEO

Tumour Heterogeneity and Intercellular Networks of Nasopharyngeal Carcinoma at Single Cell Resolution

Project description:The heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8+ T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8+ T and immune-suppressive TNFRSF4+ Treg cells in tumours might derive from peripheral CX3CR1+CD8+ T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3+ DCs. Noteworthily, intensive inter-cell interactions are observed among LAMP3+ DCs, Treg, exhausted CD8+ T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC.

2020-11-24 | GSE162025 | GEO

RNASeq of Plasmacytoid Dendritic Cells in Head and Neck Squamous Cell Cancer

Project description:<p>Plasmacytoid dendritic cells (pDC) are a subset of dendritic cells with unique immunophenotypic properties and functions. While their role in antiviral immunity through production of type I interferons is well-established, their contributions to anti-tumor immunity are less clear. While some evidence demonstrates that pDC in the tumor microenvironment (TME) may drive CD4+ T cell to become <a href="https://www.ncbi.nlm.nih.gov/gene/50943">Foxp3</a>+ T regulatory cells, little is understood about the relationship of pDC with cytotoxic CD8+ T cell, the key player in antitumor immune responses.</p> <p>In this study, we perform comprehensive immunophenotyping and functional analysis of pDC from the TME and draining lymph nodes of patients with head and neck squamous cell carcinoma (HNSCC) and identify a novel pDC subset characterized by expression of the TNF receptor superfamily member <a href="https://www.ncbi.nlm.nih.gov/gene/?term=7293">CD134 (OX40)</a>. We show that OX40 expression is expressed on intratumoral pDC in both humans and mice in a tumor-model specific fashion and that this subset of pDC enhances tumor associated-antigen (TAA)-specific CD8+ T cell responses. Through transcriptomic profiling of OX40-expressing pDC from the TME, we further characterize gene signatures unique to this pDC subset that support its role as an important immunostimulatory immune population in the TME.</p>

| phs001824 | dbGaP

Integrated multiomics profiling identifies the differentiation program of regulatory T cells in human tumors [scRNA-seq]

Project description:Regulatory T (Treg) cells suppress effective antitumor immunity in tumor-bearing hosts, thereby becoming promising targets in cancer immunotherapy. Here, we show that Treg cells in the tumor microenvironment (TME) of human lung cancers harbor a completely different open chromatin profile compared to effector T cells and peripheral Treg cells. The integrative sequencing analyses revealed that BATF, IRF4, NF-κb, and NR4A were important transcription factors for Treg cell differentiation in the TME. Particularly, BATF was identified as a key regulator, which leveraged Treg cell differentiation through epigenetically controlling activation-associated gene expression, resulting in the robustness of Treg cells in the TME. BATF deficiency in Treg cells remarkably inhibited tumor growth and high BATF expression was associated with poor prognosis in lung cancer, kidney cancer, and melanoma. Our results propose the specific chromatin remodeling and differentiation program of Treg cells in the TME, which can be applied in the development of Treg cell-targeted therapies.

2022-08-22 | GSE211068 | GEO

Integrated multiomics profiling identifies the differentiation program of regulatory T cells in human tumors [bulk ATAC-seq]

2022-08-22 | GSE211153 | GEO