Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DCBLD2 promotes perivascular anti-tumor immune deprivation by educating SPP1+ pro-angiogenic macrophages

ABSTRACT: The crosstalk between tumor vasculature and immune microenvironment underpins the anti-tumor effect of anti-angiogenic therapy (AAT) combined with immunotherapy. However, the efficacy improved by AAT in the above combination therapy is limited and its adverse effects are concerning. Integrated transcriptome and surfaceome data identified DCBLD2 as a bipotent molecule on tumor cells as a trigger for abnormal tumor vascular-immune interactions. Dcbld2 overexpression accelerated tumor growth through tumor-associated macrophages (TAMs) in preclinical mouse models. Mechanically, DCBLD2 domesticates SPP1+ pro-angiogenic TAMs through ALDH1A3-RXRG-PLK1 axis, constructing TAMs-coated vascular niches that sequester CD8+ T cell infiltration. DCBLD2 expression levels predicted the efficacy of traditional AAT in our lung cancer patient cohorts. Targeting DCBLD2 or ALDH1A3 combined with PD-1 antibody outperformed traditional AAT and immunotherapy combination. Our study identifies DCBLD2 on tumor cells as a checkpoint in abnormal vascular-immune crosstalk, offering a promising target to amplify the potency of vascular normalization and immune activation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE271377 | GEO | 2025/07/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data from in vitro-induced non-hypoxic tumour associated macrophages (TAMs)

Project description:Active immunotherapy is a promising strategy for anti-angiogenic cancer therapy. Recently, we have reported that a vaccine using human umbilical vein endothelial cells (HUVECs) induced specific anti-endothelial immune responses in the most of immunized patients, and resulted in tumor regression in some patients with recurrent malignant brain tumors, whereas not in colorectal cancer patients. In this study, we hypothesized that non-hypoxic perivascular tumor associated macrophages (TAMs) in colorectal cancer, but not in glioblastoma, might negatively alter the therapeutic efficacy of anti-angiogenic active immunotherapy. To test this hypothesis, we examined global gene expression profiles of non-hypoxic macrophages stimulated in vitro by soluble factors released from tumor cells of human glioblastoma U-87MG (‘brain TAMs’) or colorectal adenocarcinoma HT-29 (‘colon TAMs’). Murine non-hypoxic TAMs were induced in vitro by incubation with soluble factors released from human cancer cell lines U-87MG ('brain TAMs') or HT-29 ('colon TAMs'), for RNA extraction and subsequent hybridization on Affymetrix microarrays. To evaluate homogeneous macrophage populations at different tumour developmental stages, RNA aliquots of control macrophages and TAMs obtained at five different time-points, i.e. 8h, 16h, 24h, 32h and 40h, were pooled and used for screening of differentially expressed genes. The experiments for TAMs as well as for control unstimulated macrophages were performed in triplicates.

2012-03-31 | E-GEOD-18804 | biostudies-arrayexpress

Expression data from in vitro-induced non-hypoxic tumour associated macrophages (TAMs)

2012-04-01 | GSE18804 | GEO

miRseq Analysis of Human Macrophages Co-cultured with MCF-7 Breast Cancer Cells

Project description:Tumor-immune cell interactions shape the immune cell phenotype, with microRNAs (miRs) being crucial components of this crosstalk. How they are transferred, and how they affect their target landscape, especially in tumor-associated macrophages (TAMs), is largely unknown. Here we aimed to define miRome of TAMs and identify novel miRs those are deferentially expression in TAMs and decipher their functional relevance in disease settings.

2019-02-08 | E-MTAB-6885 | biostudies-arrayexpress

Therapeutic Exosomal Vaccine for Enhanced Cancer Immunotherapy by Mediating Tumor Microenvironment

Project description:Tumor immunotherapy has been convincingly demonstrated as a feasible approach for treating cancers. Although promising, however, the immunosuppressive tumor microenvironment (TME) has been recognized as a major obstacle in tumor immunotherapy. It is highly desirable to release an immunosuppressive “brake” for improving cancer immunotherapy. Among tumor-infiltrated immune cells, tumor-associated macrophages (TAMs) play an important role in the growth, invasion and metastasis of tumors. The polarization of TAMs (M2) into the M1 type can alleviate the immunosuppression of the TME and enhance the effect of immunotherapy. Inspired by this, we constructed a therapeutic exosomal vaccine from antigen-stimulated M1-type macrophages (M1OVA-Exos). M1OVA-Exos are capable of polarizing TAMs into M1 type through downregulation of the Wnt signaling pathway. Mediating the TME further activates the immune response and inhibits tumor growth and metastasis via the exosomal vaccine. Our study provides a new strategy for the polarization of TAMs, which augments cancer vaccine therapy efficacy.

2022-01-12 | GSE190619 | GEO

Mast cells decrease efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme B

Project description:Resistance towards anti-angiogenic therapy (AAT) still represents a substantial clinical challenge. We report here that tumor-infiltrating mast cells (MC) are powerful mediators decreasing efficacy of AAT in mice and cancer patients. They act in a cell-extrinsic manner by secreting granzyme B, which liberates pro-angiogenic mediators from the extracellular matrix. In addition, MC also diminish efficacy of anti-angiogenic agents in a cell-autonomous way, which can be blocked by the mast cell degranulation inhibitor cromolyn. Our findings are relevant in humans because patients harboring higher numbers of MC in their tumors have an inferior outcome after anti-angiogenic treatment in the Gepar Quinto randomized Phase 3 clinical trial. Thus, MC-targeting might represent a novel promising approach to increase efficacy of AAT.

2017-09-15 | GSE89395 | GEO

Pericyte sGC signaling dictates tumor vessel formation and tumor microenvironment

Project description:Pericytes and endothelial cells (ECs) are building blocks of blood vessels. While the contributions of ECs to tumor angiogenesis and the tumor microenvironment are well established and multiple drugs that targeting ECs have been developed for clinic use to treat cancers, the underlying mechanisms of pericyte in supporting tumor vessel and in shaping tumor microenvironment remains largely unexplored and no pericyte targeting strategies have been approved yet. This study employs targeted deletion of the NO receptor sGC in pericytes and utilizes single-cell RNA sequencing to elucidate its impact on the tumor microenvironment. The results unveil a disruptive effect on EC-pericyte interactions, subsequently impeding Notch-mediated intercellular crosstalk and prompting extensive transcriptomic reprogramming in both cell types. This vascular alteration further relays to neighboring cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) through paracrine signaling, collectively suppressing tumor growth. Importantly, the inhibition of pericyte sGC has limited influence on quiescent vessels but significantly sensitizes angiogenic vessels to anti-angiogenic treatment. In conclusion, this study underscores the vital role of pericytes in governing tumor vessels and the tumor microenvironment, suggesting that targeting pericyte sGC holds promise for enhancing anti-angiogenic therapy.

2024-02-01 | GSE243313 | GEO

Exome sequencing of KP and KPM lung tumors.

Project description:Immune checkpoint blockade (ICB) with PD1 or PDL1 antibodies has been approved for the treatment of non-small cell lung cancer (NSCLC). However, only a minority of the patients respond and sustained remissions are rare. Both chemotherapy and anti-angiogenic drugs may improve tumor response to ICB in mouse models and patients with cancer. Here, we used genetically engineered mouse models of KrasG12D/p53null NSCLC, including a mismatch repair-deficient variant (KrasG12D/p53null/Msh2null) with higher mutational burden, and longitudinal imaging to study tumor response and resistance to combinations of ICB, anti-angiogenic therapy, and chemotherapy. Anti-angiogenic blockade of VEGFA and angiopoietin-2 markedly slowed progression of established tumors but, contrary to findings in other mouse cancer models, addition of a PD1 or PDL1 antibody was not beneficial and even accelerated progression of some of the tumors. We found that anti-angiogenic treatment facilitated tumor infiltration by PD1+ regulatory T cells (T-regs), which were more efficiently targeted by the PD1 antibody than CD8+ T cells. Both tumor-associated macrophages (TAMs) of bone-marrow origin, which are CSF1R-dependent, and TAMs of alveolar origin, which are sensitive to cisplatin, contributed to establishing a TGFB-rich tumor microenvironment that supported PD1+ T-regs. Dual TAM targeting with a combination of cisplatin and a CSF1R inhibitor fully abated T-regs, redirected the PD1 antibody to CD8+ T cells, and improved the efficacy of anti-angiogenic immunotherapy, achieving regression of the majority of the tumors.

2021-08-15 | GSE169195 | GEO

Expression profile comparison of enriched bone marrow-derived tumor associated macrophages, tumor-associated alveolar macrophages, CD4 T cells, and total tumor-derived cells in lung cancer models with or without anti-PD1 and anti-VEGFA/ANGPT2 treatments.

2021-08-15 | GSE169194 | GEO

PAD4 controls tumor immunity via restraining the MHC-II machinery in macrophages

Project description:Tumor-associated macrophages (TAMs) shape tumor immunity and therapeutic efficacy. However, it is poorly understood if and how post-translational modifications (PTMs) intrinsically affect the phenotype and function of TAMs. Here, we found that peptidylarginine deiminase 4 (PAD4) manifested the highest expression among common PTM enzymes in TAMs and negatively correlated to clinical response to immune checkpoint blockade (ICB). Genetic and pharmacological inhibition of PAD4 in macrophages prevented tumor progression in tumor-bearing mouse models, accompanied by an increase in macrophage MHC-II expression and T-cell effector function. Mechanistically, PAD4 citrullinated STAT1 at arginine 121 (R121), thereby promoting the interaction between STAT1 and PIAS1; and the loss of PAD4 abolished this interaction, ablating the inhibitory role of PIAS1 in the expression of MHC-II machinery in macrophages and enhancing T-cell activation. Thus, the PAD4-STAT1-PIAS1 axis is a previously unknown intrinsic immune restriction mechanism in macrophages and may serve as a cancer immunotherapy target.

2024-05-22 | PXD049188 | Pride

Glioma-neuronal circuit remodeling induces regional immunosuppression [RNA-Seq]

Project description:Neuronal activity-driven mechanisms impact glioblastoma cell proliferation and invasion (1–7), and glioblastoma remodels neuronal circuits (8,9). Distinct intratumoral regions maintain functional connectivity via a subpopulation of malignant cells that mediate tumor-intrinsic neuronal connectivity and synaptogenesis through their transcriptional programs (8). However, the effects of tumor-intrinsic neuronal activity on other cells, such as immune cells, remain unknown. Here we show that regions within glioblastomas displaying elevated connectivity are characterized by regional immunosuppression. This is accompanied by different cell compositions and inflammatory status of tumor-associated macrophages (TAMs) in the tumor microenvironment. In preclinical models, genetic knockout of Thrombospondin-1 (TSP1/Thbs1), a synaptogenic factor critical for glioma-induced neuronal circuit remodeling, in glioblastoma cells suppressed synaptogenesis and glutamatergic neuronal hyperexcitability. Moreover, this restored antigen-presentation and pro-inflammatory responses, promoted the infiltration of pro-inflammatory TAMs and CD8+ T-cells, and mitigated the immunosuppressive effect of TAMs on T-cell proliferation. Furthermore, pharmacological inhibition of glutamatergic excitatory neuronal signaling redirected TAMs toward a less immunosuppressive phenotype, resulting in prolonged mouse survival. Lastly, pharmacological inhibition of glutamatergic signaling showed potential to enhance the efficacy of immune cell-based therapy. Altogether, our results demonstrate previously unrecognized immunosuppression mechanisms resulting from glioma-neuronal circuit remodeling and suggest that targeting glioma-neuron-immune crosstalk could provide new avenues for immunotherapy.

2025-03-18 | GSE289935 | 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