Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

FAM114A1 Promotes Immune Evasion of Triple-negative Breast Cancer by Simultaneously Activating PI3K/AKT Signaling and Disrupting E2F4-condensate Formation

ABSTRACT: Immune checkpoint blockade (ICB) therapy, which revolutionized cancer treatment, has been approved for triple-negative breast cancer (TNBC) treatment. Unfortunately, the majority of TNBC patients are either not eligible for the treatment or exhibit resistance. Understanding the underlying mechanisms and enhancing treatment efficacy are urgently needed. Here, utilizing CRISPR activation screening, we identified FAM114A1 as a key mediator of immune evasion and ICB therapy resistance in TNBC patients. Mechanistically, FAM114A1 binds to p85α to activate PI3K/AKT pathway, and simultaneously, prevents E2F4-condensate formation to promote E2F4-driven MTDH expression. Elevation of these FAM114A1-mediated pathways inhibit tumor antigen presentation and consequently suppress anti-tumor immunity in TNBC. Moreover, FAM114A1-targeting boosts anti-PD-1 treatment in mouse models and the FAM114A1 signature shows strong predictive performance in recognizing TNBC patients who may benefit from ICB therapy. Collectively, our study provides new insights into the mechanisms underlying TNBC immune evasion and a potential avenue to improve ICB treatment effectiveness.

ORGANISM(S): Mus musculus

PROVIDER: GSE295176 | GEO | 2025/10/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

TLR4-dependent fibroblast-monocyte axis in tumor-draining lymph nodes contributes to metastasis in triple-negative breast cancer

Project description:Triple-negative breast cancer (TNBC) is the most aggressive form of BC and despite improvements in neoadjuvant treatment with immune checkpoint blockade (ICB) targeting PD-1, response rates vary, and patients relapse with metastatic disease. Using human samples and mouse models, we show that myeloid cells, particularly monocytes, increase in aggressive TNBC draining lymph nodes (TDLN) showing T-cell suppressive capacity via PD-L1 and iNOS. Tumor-induced TLR4 ligands reprogrammed TDLN fibroblastic reticular cells (FRCs) through TLR4 activation to induce the recruitment of monocytes via CCL2 and CCL7 in vascularized and T-cell areas. Indeed, monocytes expressing the receptor of CCL2/7 CCR2 home to and colocalize with FRC-rich niches. The local inhibition of this recruitment axis at the TDLN site, either through CCR2 or TLR4 inhibition, in combination with PD-1 blocking, resulted in reduced LN and distant lung metastasis in mouse models. A subset of TNBC patients with worse survival was stratified using TLR4 ligands, including TNC, S100A9, and FN1. Our results thus demonstrate a novel mechanism through which metastatic TNBC tumors reprogram the TDLN-niche to facilitate PD-L1-mediated immune evasion that precedes and drives metastasis. We thereby provide an opportunity to improve the efficacy of ICB in TNBC patients and to use the TDLN or our primary tumor signature as predictive biomarkers.

2025-09-17 | GSE267535 | GEO

TLR4-dependent fibroblast-monocyte axis in tumor-draining lymph nodes contributes to metastasis in triple-negative breast cancer

2025-09-17 | GSE267534 | GEO

TLR4-dependent fibroblast-monocyte axis in tumor-draining lymph nodes contributes to metastasis in triple-negative breast cancer

2025-09-17 | GSE267533 | GEO

PABPC1L promotes tryptophan metabolism and immune suppression by stabilizing IDO1 in renal cell carcinoma

Project description:The tumor microenvironment (TME) in renal cell carcinomas (RCC) is marked by substantial immunosuppression and immune resistance though highly infiltrated by T cells. There is an urgent need to elucidate tumor immune evasion and to develop novel therapeutic target to boost the efficacy of immune checkpoint blockade (ICB) in RCC. Our study uncovers a mechanism wherein the polyadenylate-binding protein PABPC1L modulates indoleamine2, 3dioxygenase1 (IDO1), a prospective candidate for immunotherapy. PABPC1L, markedly upregulated in RCC, correlates with unfavorable prognosis and resistance to ICB. Overexpressed PABPC1L bolsters tryptophan metabolism and induces T-cell dysfunction by stabilizing IDO1. Conversely, silencing PABPC1L diminishes IDO1 expression, mitigates cytotoxic T-cell suppression, and enhances responsiveness to anti-PD-1 therapy. Our findings underscore PABPC1L's crucial role in facilitating immune evasion in RCC, making it a potential addition to ICB therapy.

2024-02-14 | GSE241871 | GEO

PABPC1L promotes tryptophan metabolism and immune suppression by stabilizing IDO1 in renal cell carcinoma [RIP-seq]

2024-02-14 | GSE255448 | GEO

Tumor immunological phenotype signature-based high-throughput screening for the discovery of combination immunotherapy compounds

Project description:Immune checkpoint blockade (ICB) therapy intends to only benefit a fraction of cancer patients, and combination immunotherapy with a compound is a promising treatment to overcome this limitation. Here, a tumor immunological phenotype (TIP) gene signature and high throughput sequencing-based high throughput screening (HTS2) were combined to identify combination immunotherapy compounds. We firstly defined a TIP gene signature, which expression pattern distinguishes “cold” tumors from “hot” tumors, and predicts ICB response in cancer patients. Then, after screening thousands of compounds, we identified that aurora kinase inhibitors, including ENMD-2076 and TAK-901, could reprogram the expression pattern of TIP genes from “cold” tumor to “hot” tumor in triple negative breast cancer (TNBC) cells. The treatment of aurora kinase inhibitors on TNBC cells dramatically up-regulates expression of Th1 type chemokine genes CXCL10 and CXCL11, which promotes effective T cells infiltrating into tumor microenvironment and significantly improves anti-PD-1 efficacy in inhibiting the tumor growth of TNBC in preclinical models. Mechanistically, these aurora kinase inhibitors are mainly through inhibiting AURKA-STAT3 signaling pathway to stimulate the expression of CXCL10 and CXCL11. Our study established a high throughput strategy to discover candidate compounds for combination immunotherapy, and suggested the therapeutic potential of combining aurora kinase inhibitors with checkpoint blockade immunotherapy for the treatment of TNBC.

2020-12-31 | GSE160071 | GEO

Immunologic and clinical activity to ICB combinations in DAPPER Leiomyosarcoma cohort

Project description:Non-inflamed (cold) tumors such as leiomyosarcoma (LMS) do not benefit from immune checkpoint blockade (ICB) monotherapy. Combining ICB with angiogenesis-, or poly-ADP ribose polymerase (PARP) inhibitors may increase tumor immunogenicity by altering the immune cell composition of the tumor microenvironment (TME). The DAPPER phase II study evaluated the safety, immunologic, and clinical activity of ICB-based combinations in pre-treated LMS patients.

2024-01-01 | E-MTAB-12922 | biostudies-arrayexpress

CEBPB-high dormant tumor cells drive immune evasion [ChIP-Seq]

Project description:Triple negative breast cancer (TNBC) poorly responds to immune checkpoint blockade (ICB) therapy. Dormant tumor cells are recognized as immunotherapy-resistant reservoirs, potential leading to tumor relapse, highlighting the importance to elucidate the mechanisms underlying immunotherapy resistance. Herein, we demonstrated that dormant tumor cells were resistant to ICB therapy and occupied an immunosuppressive niche with enhanced tumor-associated macrophages (TAMs) and decreased CD8+T cells infiltration in mouse TNBC allografts via a label-retention system. CEBPB was highly expressed in dormant tumor cells and maintained tumor dormancy by transcriptionally activating cell cycle negative regulators like CCNG2 and p27.

2025-02-21 | GSE290039 | GEO

CEBPB-high dormant tumor cells drive immune evasion [RNA-Seq]

2025-02-21 | GSE290038 | GEO

USP5 stabilizes YTHDF1 to control cancer immune surveillance through mTORC1-mediated phosphorylation

Project description:N6-methyladenosine (m6A) binding protein YTHDF1 is frequently upregulated in various cancers and its depletion enhances the efficacy of immune checkpoint blockade (ICB) therapy. This study reveals that USP5 interacts with YTHDF1, preventing its K11-linked polyubiquitination, thereby stabilizing YTHDF1 and promoting its oncogenic properties. In response to insulin, mTORC1 phosphorylates USP5, facilitating its dimerization and subsequent binding to YTHDF1, while the CUL7-FBXW8 complex promotes its degradation. Notably, YTHDF1 or USP5 deficiency increases PD-L1 expression and impairs immune response gene expression, contributing to immune evasion. Combining USP5 inhibitors with anti-PD-1 therapy enhances antitumor T-cell immunity and improves tumor regression in mouse models. Thus, USP5 may serve as a biomarker for stratifying patients for anti-PD-1 therapy, suggesting a novel strategy of combining USP5 inhibition with PD-(L)1 blockade to enhance cancer treatment efficacy.

2024-12-05 | GSE278264 | 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