Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Quiescent cancer cells resist T cell attack by forming an immunosuppressive niche (QCC vs proliferative cells from tumors Bulk RNA)

ABSTRACT: Immunotherapy is a promising treatment for Triple-Negative Breast Cancer (TNBC), but patients recur, arising the need to understand mechanisms of resistance. We discovered that in primary breast cancer, tumor cells that survive T-cell attack are in a quiescent state. Quiescent Cancer Cells (QCCs) are found clustering together forming regions with reduced immune infiltration. QCCs display superior tumorigenic capacity and higher expression of stemness genes than their proliferative counterparts. We adapted single-cell-RNA-sequencing with precise spatial resolution to profile infiltrating cells inside and outside QCC niches. This transcriptomic analysis revealed hypoxia-induced programs and identified more exhausted T-cells, tumor-protective fibroblasts, and dysfunctional dendritic cells inside clusters of QCCs. This uncovered differential phenotypes in infiltrating cells based on their specific intra-tumor location. Thus, QCCs constitute immunotherapy-resistant reservoirs by orchestrating a local hypoxic immune-suppressive milieu that blocks T-cell function. Eliminating QCCs holds the promise to counteract resistance to immunotherapy and prevent disease recurrence in TNBC.

ORGANISM(S): Mus musculus

PROVIDER: GSE198713 | GEO | 2022/04/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Quiescent cancer cells resist T cell attack by forming an immunosuppressive niche (PADMEseq)

Project description:Immunotherapy is a promising treatment for Triple-Negative Breast Cancer (TNBC), but patients recur, arising the need to understand mechanisms of resistance. We discovered that in primary breast cancer, tumor cells that survive T-cell attack are in a quiescent state. Quiescent Cancer Cells (QCCs) are found clustering together forming regions with reduced immune infiltration. QCCs display superior tumorigenic capacity and higher expression of stemness genes than their proliferative counterparts. We adapted single-cell-RNA-sequencing with precise spatial resolution to profile infiltrating cells inside and outside QCC niches. This transcriptomic analysis revealed hypoxia-induced programs and identified more exhausted T-cells, tumor-protective fibroblasts, and dysfunctional dendritic cells inside clusters of QCCs. This uncovered differential phenotypes in infiltrating cells based on their specific intra-tumor location. Thus, QCCs constitute immunotherapy-resistant reservoirs by orchestrating a local hypoxic immune-suppressive milieu that blocks T-cell function. Eliminating QCCs holds the promise to counteract resistance to immunotherapy and prevent disease recurrence in TNBC.

2022-04-20 | GSE198714 | GEO

Quiescent cancer cells resist T cell attack by forming an immunosuppressive niche (GFP:mCherry 1:1 4T07 mix tumors after Jedi killing Bulk RNA)

2022-04-20 | GSE198712 | 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

Breast cancer-subtype and infiltrating macrophage signatures predict chemotherapy-response and survival

Project description:Triple-Negative Breast Cancer (TNBC) is a heterogeneous collection of cancers where personalized treatment is difficult and chemotherapy and immunotherapy combinations are the main treatment options. Many attempts to tackle patient heterogeneity have focused on defining cancer-intrinsic subtypes based on differential tumor mRNA-expression across patient cohorts. While these multi-gene diagnostics have shown success in hormone receptor- positive cancers (e.g. OncotypeDX), no TNBC classifiers have shown clinical utility in predicting patient survival or treatment response. We hypothesize that TNBC-infiltrating immune-cells both affect mRNA-based classification and contribute to treatment response variability. To evaluate this hypothesis, we benchmarked the performance of common TNBC-classification (TNBC-type) and infiltrating immune (CIBERSORT) algorithms on the same underlying datasets. Encouragingly, we found that – as with OncotypeDx– highly proliferative TNBC-subtypes (BL1) show the strongest evidence of response to cytotoxic chemotherapies. Interestingly, this cancer-proliferative signature (BL1) is strongly correlated with enrichment in tumor-infiltrating lymphocyte signatures (TIL) which show superior prognostic and predictive power. In addition, Tumor Associated Macrophage (TAM) signatures show independent predictive and prognostic power for both patient survival and response to anthracycline- and taxane-based chemotherapies. These gene signature-based correlations were validated in a new independent cohort of 67 TNBC-patients treated with neoadjuvant chemotherapy. Overall, these results argue for the independent contributions of both cancer-intrinsic and -extrinsic factors in predicting treatment response in the neoadjuvant setting.

2024-03-20 | GSE260693 | GEO

Quiescent cancer cells resist T cell attack by forming an immunosuppressive niche

Project description:Quiescent cancer cells resist T cell attack by forming an immunosuppressive niche

| PRJNA816518 | ENA

Quiescent cancer cells resist T cell attack by forming an immunosuppressive niche (PADMEseq)

Project description:Quiescent cancer cells resist T cell attack by forming an immunosuppressive niche (PADMEseq)

| PRJNA816524 | ENA

Breast cancer stem cell-derived tumors escape from γδ T cell immunosurveillance in vivo by modulating γδ T cell ligands

Project description:Triple negative breast cancer (TNBC) lacks targeted therapy options. TNBC is enriched in breast cancer stem cells (BCSCs), which play a key role in metastasis, chemoresistance, relapse and mortality. γδ T cells hold great potential in immunotherapy against cancer, and might be an alternative to target TNBC. γδ T cells are commonly observed to infiltrate solid tumors and have an extensive repertoire of tumor sensing, recognizing stress-induced molecules and phosphoantigens (pAgs) on transformed cells. We show that patient derived triple negative BCSCs are efficiently recognized and killed by ex vivo expanded γδ T cells from healthy donors. Orthotopically xenografted BCSCs, however, were refractory to γδ T cell immunotherapy. Mechanistically, we unraveled concerted differentiation and immune escape: xenografted BCSCs lost stemness, expression of γδ T cell ligands, adhesion molecules and pAgs, thereby evading immune recognition by γδ T cells. Indeed, neither pro-migratory engineered γδ T cells, nor anti-PD 1 checkpoint blockade significantly prolonged overall survival of tumor-bearing mice. BCSC immune escape was independent of the immune pressure exerted by the γδ T cells, and could be pharmacologically reverted by Zoledronate or IFN-α treatment. These results pave the way for novel combinatorial immunotherapies for TNBC.

2023-07-20 | PXD039463 | Pride

JAML is a novel immunotherapy target for tissue-resident memory T cells [scRNA-seq]

Project description:Tumor-infiltrating CD8+ T cells express high levels of the co-stimulatory molecule JAML, which can be exploited for cancer immunotherapy.

2023-08-08 | GSE185161 | GEO

JAML is a novel immunotherapy target for tissue-resident memory T cells [bulk RNA-seq]

Project description:Tumor-infiltrating CD8+ T cells express high levels of the co-stimulatory molecule JAML, which can be exploited for cancer immunotherapy.

2023-08-08 | GSE185160 | GEO

Tumor infiltrating exhausted CD8+ T cells dictate divergent survival outcomes in pre- versus post-menopausal estrogen receptor-positive breast cancer

Project description:CD8+ tumor infiltrating lymphocytes (TILs) are associated with improved survival in triple negative breast cancer (TNBC), yet have no association with survival in estrogen receptor-positive (ER+) BC. The basis for these contrasting findings remains elusive. We identify subsets of BC tumors infiltrated by CD8+ T cells with characteristic features of exhausted T cells (TEX). Tumors with abundant CD8+ TEX exhibit a distinct tumor microenvironment marked by amplified interferon-γ signaling related pathways and higher PD-L1 expression. Paradoxically, high levels of CD8+ TEX TILs associate with decreased overall survival ER+ BC patients, but not TNBC patients. Moreover, high tumor expression of a CD8+ TEX signature identifies dramatically reduced survival in pre-menopausal, but not post-menopausal, ER+ BC patients. Finally, we demonstrate the value of a tumor TEX signature score in identifying high-risk pre-menopausal ER+ BC patients amongst those with intermediate Oncotype Dx breast recurrence scores. Our data highlight the complex relationship between CD8+ TILs, interferon-γ signaling, and estrogen receptor status in BC patient survival. This work identifies pre-menopausal ER+ BC patients with high levels of tumor infiltrating CD8+ TEX as a high-risk subset that may benefit from immunotherapy strategies.

2022-02-23 | GSE190202 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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