Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regulatory T cells Restrain CD4 T Cell Control of MHC-I-Deficient Metastatic Pancreatic Cancer Emerging After PD-L1 Blockade [scRNA-seq]

ABSTRACT: We investigate mechanisms of immunotherapy resistance in pancreatic cancer. PD-L1 blockade selects for metastatic tumor variants with defective IFNγ-inducible MHC-I due to epigenetic silencing of Tap1. Restoring MHC-I limits primary tumor growth but fails to prevent metastasis. In contrast, regulatory T cell (TREG) depletion suppresses metastasis by unleashing CD4 T helper cells. Adoptive transfer of tumor-specific CD4 T cells impairs metastatic progression. Tumor-specific CD4 T cells in lymph nodes preferentially adopt a TCF1⁺SLAMF6⁺ precursor state. Intratumoral TREG targeting with anti–CTLA-4 abrogates metastasis, drives accumulation of stem-like, tissue-resident helper CD4 T cells, producing a gene signature associated with improved patient outcomes. Combined CTLA-4 blockade and MHC-I restoration eliminates metastasis and prolongs animal survival. In human tumors, TREG and CD4 helper T cells co-localize and correlate with both tumor MHC-I expression and overall survival. Together, these findings identify actionable mechanisms of immune evasion and metastasis in immunotherapy-resistant cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE330011 | GEO | 2026/06/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Regulatory T cells Restrain CD4 T Cell Control of MHC-I-Deficient Metastatic Pancreatic Cancer Emerging After PD-L1 Blockade [ATAC-seq]

Project description:We investigate mechanisms of immunotherapy resistance in pancreatic cancer. PD-L1 blockade selected for metastatic tumor variants with defective IFN-g–inducible MHC-I due to epigenetic Tap1 silencing. Restoration of MHC-I limited primary tumor growth but failed to prevent metastasis. In contrast, regulatory T cell (TREG) depletion abrogated metastasis by unleashing conventional CD4 T cells. Metastasis was also mitigated by transfer of tumor-reactive CD4 T cells or by CTLA-4 blockade. Tumor-specific CD4 T cells adopt a TCF1⁺SLAMF6⁺ progenitor state in lymph nodes and further differentiate in malignant sites. CTLA4 blockade abrogated metastasis, drove intratumoral accumulation CD4 T cells with stemness and tissue residency features, producing a gene signature correlating with improved patient outcomes. MHC-I restoration with anti-CTLA4 prolonged animal survival. TREG and CD4 T cells co-localized in human tumors and abundance correlated with tumor MHC-I and overall survival. Together, these findings identify actionable mechanisms of immune evasion and metastasis in immunotherapy-resistant cancer.

2026-06-26 | GSE330482 | GEO

Regulatory T cells Restrain CD4 T Cell Control of MHC-I-Deficient Metastatic Pancreatic Cancer Emerging After PD-L1 Blockade [EM-Seq]

2026-06-26 | GSE330323 | GEO

Circulating cell populations as response predictors and targets to improve immunotherapy in metastatic lung cancer

Project description:<p>The effectiveness of immunotherapy varies among patients with advanced non-small cell lung cancer (NSCLC). Here we investigated the baseline immune status in stage IV NSCLC patients treated with anti-PD-1 plus chemotherapy to understand the immune mechanisms and unveil systemic markers associated with treatment response. Responders had elevated frequencies of circulating T cells expressing CD69, TCF-1 and CXCR-3. In contrast, non-responders presented increased frequencies of CTLA-4, CD161 and IL-10 expressing CD4+ and CD8+ T cells. These systemic T cell immune profiles were mirrored in the tumor microenvironment of an independent cohort. Concurrent CTLA-4 and PD-1 blockade was able to reactivate an anti-tumor profile in T cells from non-responder patients, emphasizing the pivotal role of CTLA-4 in contributing to an immunosuppressive environment that hinders effective treatment in NSCLC. This work supports the implementation of personalized immunotherapies based on systemic immune biomarkers, offering a promising approach to enhance treatment outcomes in advanced NSCLC.</p>

2025-10-16 | MTBLS13150 | MetaboLights

Intratumoral anti-CTLA-4 delivery by an oncolytic Vaccinia virotherapy virus elicits CD8+ T cell immunity and synergizes with anti-PD-1 to reject “cold” tumors

Project description:CTLA-4 is a clinically validated antibody target for cancer immunotherapy. Toxicity, which is linked to efficacy in available anti-CTLA-4 regimens has, however, restricted their use and precluded full therapeutic dosing. Here we describe and preclinically characterize a potentially safe and highly efficacious strategy to target CTLA-4. Intratumoral administration of an oncolytic Vaccinia virus, engineered to encode a novel Treg depleting, checkpoint-blocking, anti-CTLA-4 antibody and GM-CSF (VVGM-aCTLA4) achieved tumor-restricted CTLA-4 receptor saturation and Treg-depletion, and regressed diverse tumors spanning inflamed to immunologically ignorant microenvironments. Critically, intratumorally “ignited” antitumor immunity translated into stronger systemic expansion of tumor-specific CD8+ T cells compared with systemic anti-CTLA-4. In a clinically relevant mouse model resistant to systemic immune checkpoint blockade, i.t. VVGM-aCTLA4 synergized with anti-PD-1 to reject “cold” tumors. Based on our established proof-of-concept, a clinical trial evaluating i.t. VVGM-aCTLA4 (BT-001) alone and in combination with anti-PD-1 in metastatic or advanced solid tumors has commenced.

2022-02-08 | GSE176052 | GEO

T cell oxygen-sensing proteins establish an immunologically tolerant metastatic niche

Project description:Cancer cells must evade immune responses at distant sites to establish metastases. The lung is a frequent site for metastasis. We hypothesized that lung-specific immunoregulatory mechanisms create an immunologically permissive environment for tumor colonization. We found that T cell-intrinsic expression of the oxygen-sensing prolyl-hydroxylase (PHD) proteins is required to maintain local tolerance against innocuous antigens in the lung, but powerfully licenses colonization by circulating tumor cells. PHD proteins limit pulmonary type helper (Th)-1 responses, promote CD4+-regulatory T (Treg) cell induction, and restrain CD8+ T cell effector function. Tumor colonization is accompanied by PHD protein-dependent induction of pulmonary Treg cells and suppression of IFN-g-dependent tumor clearance. T cell-intrinsic deletion or pharmacological inhibition of PHD proteins limits tumor colonization of the lung and improves the efficacy of adoptive cell transfer immunotherapy. Collectively, PHD proteins function in T cells to coordinate distinct immunoregulatory programs within the lung that are permissive to cancer metastasis. RNA expression was measured by RNA-Seq at day 4 following stimulation of naÃ¯ve FACS-sorted CD4+ T cells with anti-CD3 and anti-CD28 antibodies in the presence of indicated doses of TGF-b. Gene expression was analysed separately in control Cd4Cre (WT) and Egln1fl/fl Egln2fl/fl Egln3fl/fl Cd4Cre (tKO) cells, or in cells treated with the pharmacological PHD inhibitor dimethyloxaloylglycine (DMOG) and control vehicle-treated cells.

2016-08-03 | E-GEOD-85131 | biostudies-arrayexpress

High-dimensional single cell analysis of T cells infiltrating human intrahepatic cholangiocarcinoma [scRNA-Seq]

Project description:In tumors, CD4+ T regulatory cells (Tregs), a specialized subtype of cells indispensable for maintaining immune homeostasis and tolerance, inhibit anti-tumor immunity and response to immunotherapy. Selective targeting of the hyperactive Tregs promote tumor regression and synergizes with checkpoint blockade without severe, systemic autoimmunity, that is otherwise observed with non-specific Treg depletion. However, is poorly defined how Treg hyper-activation regulated in the tumor microenvironment. We found that mesenchyme homeobox-1 (MEOX1) a transcription factor with an important role in skeleton formation during development, is specifically overexpressed by intrahepatic cholangiocarcinoma infiltrating Treg compared to Treg cells present in the peritumoral tissue. Integration of transcriptomic data revealed that MEOX1 positively regulates several molecules involved in immunosuppression, including CTLA-4, ICOS and IL10, as well as a tumor Treg-specific signature associated with disease progression. Thus, interfering with the MEOX1-dependent molecular program may represent a novel immunotherapeutic approach capable to block immunosuppression in the tumor microenvironment without inducing autoimmunity in peripheral tissues.

2022-06-30 | GSE171899 | GEO

High-dimensional single cell analysis of T cells infiltrating human intrahepatic cholangiocarcinoma [RNA-Seq]

2022-06-30 | GSE171895 | GEO

CTLA-4 blockade enhances germinal center reactions in lymph nodes that drive glioma-specific IgG production and glioma clearance

Project description:Humoral immunity, which is mediated by B cells that mature in germinal centers (GCs) in lymph nodes (LNs), is essential for adaptive immune responses. However, the involvement of B cell responses in anti-tumor and immunotherapy responses remains largely unexplored. Here, we show that activation of B cells in GCs of tumor-draining deep cervical LNs (dcLNs) is necessary for the efficacy of CTLA-4 immune checkpoint blockade in glioma in vivo. We demonstrate that anti-CTLA-4 therapy enhances follicular helper T cell (Tfh) expansion in dcLNs, leading to GC B cell formation, class switching to IgG, and the generation of glioma-specific antibodies. Glioma-bearing mice lacking antibody-secreting cells did not benefit from CTLA-4 blockade. Furthermore, using our new in vivo reporter system, we show that distally-secreted glioma-specific IgG infiltrates the tumor microenvironment and triggers glioma cell phagocytosis. Our study uncovers a previously unknown B cell–dependent mechanism underlying anti-CTLA-4 mediated control of glioma, which could be harnessed to treat other tumor types.

2026-05-28 | GSE315742 | GEO

Combination LIGHT overexpression and checkpoint blockade disrupts the tumor immune environment eradicating colorectal liver metastases

Project description:Liver metastases contribute to resistance to cancer immunotherapy across tumor types and thus disrupting the immunosuppressive microenvironment of liver metastases is a therapeutic challenge. The expression of LIGHT, an immunostimulatory cytokine, can increase tumor-infiltrating T cells into colorectal cancer liver metastases and form tertiary lymphoid structures. We investigated the effect of combined anti-CTLA-4 and LIGHT expression in a mouse model of liver metastasis, demonstrating synergistic effects on tumor control, Treg-mediated suppression, and T cell activation, proliferation, and exhaustion. While intratumoral LIGHT or anti-CTLA-4 alone induced tumor-associated macrophages (TAM), only the combination led to a decrease in TAM and MDSC populations and activation of dendritic cells. The combination of LIGHT and anti-CTLA-4 represents a strategy of overcoming immunosuppression in colorectal cancer as well as other microsatellite stable tumors in which liver metastases drive resistance to immunotherapy.

2025-08-29 | GSE252597 | GEO

In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases [scRNA-seq TCR]

Project description:Liver metastases are associated with poor response to current pharmacological treatments, including immunotherapy. We describe a lentiviral vector (LV) platform to selectively engineer liver macrophages, including Kupffer cells and tumor-associated macrophages (TAMs), to deliver type I interferon (IFNα) to liver metastases. Gene-based IFNα delivery delays the growth of colorectal and pancreatic ductal adenocarcinoma liver metastases in mice. Response to IFNα is associated with TAM immune activation, enhanced MHC-II-restricted antigen presentation and reduced exhaustion of CD8+ T cells. Conversely, increased IL-10 signaling, expansion of Eomes CD4+ T cells, a cell type displaying features of type I regulatory T (Tr1) cells, and CTLA-4 expression are associated with resistance to therapy. Targeting regulatory T cell functions by combinatorial CTLA-4 immune checkpoint blockade and IFNα LV delivery expands tumor-reactive T cells, attaining complete response in most mice. These findings support a promising therapeutic strategy with feasible translation to patients with unmet medical need.

2023-10-17 | GSE245453 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data