Spatial multi-omics analysis of tumor-stroma boundary cell features for predicting breast cancer progression and therapy response DOI Creative Commons
Yuanyuan Wu, Youyang Shi,

Zhanyang Luo

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 26, 2025

Background The tumor boundary of breast cancer represents a highly heterogeneous region. In this area, the interactions between malignant and non-malignant cells influence progression, immune evasion, drug resistance. However, spatial transcriptional profile its role in prognosis treatment response remain unclear. Method Utilizing Cottrazm algorithm, we reconstructed intricate boundaries identified differentially expressed genes (DEGs) associated with these regions. Cell-cell co-positioning analysis was conducted using SpaCET, which revealed key tumor-associated macrophage (TAMs) cancer-associated fibroblasts (CAFs). Additionally, Lasso regression employed to develop body signature (MBS), subsequently validated TCGA dataset for prediction assessment. Results Our research indicates that is characterized by rich reconstruction extracellular matrix (ECM), immunomodulatory regulation, epithelial-to-mesenchymal transition (EMT), underscoring significance progression. Spatial colocalization reveals significant interaction CAFs M2-like (TAM), contributes exclusion MBS score effectively stratifies patients into high-risk groups, survival outcomes exhibiting high scores being significantly poorer. Furthermore, sensitivity demonstrates high-MB tumors had poor chemotherapy strategies, highlighting modulating therapeutic efficacy. Conclusion Collectively, investigate transcription group bulk data elucidate characteristics molecules cancer. CAF-M2 phenotype emerges as critical determinant immunosuppression resistance, suggesting targeting may improve responses. serves novel prognostic tool offers potential strategies guiding personalized approaches

Language: Английский

How chemokines organize the tumour microenvironment DOI
Thorsten R. Mempel, Julia K. Lill, Lukas M. Altenburger

et al.

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 24(1), P. 28 - 50

Published: Dec. 8, 2023

Language: Английский

Citations

95

Notch signaling pathway in cancer: from mechanistic insights to targeted therapies DOI Creative Commons

Qingmiao Shi,

Chen Xue,

Yifan Zeng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 27, 2024

Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The receptor ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical signaling transduction. Accumulating evidence indicates that the pathway serves as both an oncogenic factor a tumor suppressor various cancer types. Dysregulation of this promotes epithelial-mesenchymal transition angiogenesis malignancies, closely linked proliferation, invasion, metastasis. Furthermore, contributes maintaining stem-like properties cells, thereby enhancing invasiveness. regulatory metabolic reprogramming microenvironment suggests pivotal involvement balancing suppressive effects. Moreover, implicated conferring chemoresistance cells. Therefore, comprehensive understanding these biological processes crucial developing innovative therapeutic strategies targeting signaling. This review focuses on research progress cancers, providing in-depth insights into potential mechanisms regulation occurrence progression cancer. Additionally, summarizes pharmaceutical clinical trials therapy, aiming offer new human malignancies.

Language: Английский

Citations

84

Advances in spatial transcriptomics and related data analysis strategies DOI Creative Commons

Jun Du,

Yuchen Yang, Zhijie An

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 18, 2023

Spatial transcriptomics technologies developed in recent years can provide various information including tissue heterogeneity, which is fundamental biological and medical research, have been making significant breakthroughs. Single-cell RNA sequencing (scRNA-seq) cannot spatial information, while allow gene expression to be obtained from intact sections the original physiological context at a resolution. Various insights generated into architecture further elucidation of interaction between cells microenvironment. Thus, we gain general understanding histogenesis processes disease pathogenesis, etc. Furthermore, silico methods involving widely distributed R Python packages for data analysis play essential roles deriving indispensable bioinformation eliminating technological limitations. In this review, summarize available transcriptomics, probe several applications, discuss computational strategies raise future perspectives, highlighting developmental potential.

Language: Английский

Citations

73

Cancer organoids 2.0: modelling the complexity of the tumour immune microenvironment DOI
Roel Polak, Elisa Zhang, Calvin J. Kuo

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(8), P. 523 - 539

Published: July 8, 2024

Language: Английский

Citations

48

Fully automated sequential immunofluorescence (seqIF) for hyperplex spatial proteomics DOI Creative Commons
François Rivest, Deniz Eroglu,

Benjamin Pelz

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Oct. 9, 2023

Tissues are complex environments where different cell types in constant interaction with each other and non-cellular components. Preserving the spatial context during proteomics analyses of tissue samples has become an important objective for applications, one most being investigation tumor microenvironment. Here, we describe a multiplexed protein biomarker detection method on COMET instrument, coined sequential ImmunoFluorescence (seqIF). The fully automated uses successive applications antibody incubation elution, in-situ imaging enabled by integrated microscope microfluidic chip that provides optimized optical access to sample. We show seqIF data sample such as healthy tissue, including 40-plex single section is obtained less than 24 h, using off-the-shelf antibodies. also present extensive characterization developed method, elution efficiency, epitope stability, repeatability reproducibility, signal uniformity, dynamic range, addition marker panel optimization strategies. streamlined workflow antibodies, quality enabling downstream analysis, ease reaching hyperplex levels make suitable immune-oncology research disciplines requiring paving way its adoption clinical settings.

Language: Английский

Citations

43

Open-ST: High-resolution spatial transcriptomics in 3D DOI

Marie Schott,

Daniel León-Periñán, Elena Splendiani

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(15), P. 3953 - 3972.e26

Published: June 24, 2024

Language: Английский

Citations

37

Multiplex protein imaging in tumour biology DOI
Natalie de Souza, Shan Zhao, Bernd Bodenmiller

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(3), P. 171 - 191

Published: Feb. 5, 2024

Language: Английский

Citations

30

Gastric cancer immunosuppressive microenvironment heterogeneity: implications for therapy development DOI
Tadahito Yasuda, Yanru Wang

Trends in cancer, Journal Year: 2024, Volume and Issue: 10(7), P. 627 - 642

Published: April 9, 2024

Language: Английский

Citations

30

Advances in Engineered Macrophages: A New Frontier in Cancer Immunotherapy DOI Creative Commons
Shuaixi Yang, Yuhang Wang,

Jiachi Jia

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)

Published: April 1, 2024

Abstract Macrophages, as pivotal cells within the tumour microenvironment, significantly influence impact of and reactions to treatments for solid tumours. The rapid evolution bioengineering technology has revealed vast potential engineered macrophages in immunotherapy, disease diagnosis, tissue engineering. Given this landscape, goal harnessing innovating a novel strategy immunotherapy cannot be overstated. diverse strategies realm cancer encompassing macrophage drug delivery systems, chimeric antigen receptor therapy, synergistic treatment approaches involving bacterial outer membrane vesicles macrophages, are meticulously examined review. These methodologies designed enhance therapeutic efficacy against tumours, particularly those that drug-resistant metastatic. Collectively, these immunotherapies poised supplement refine current paradigms, thus heralding new frontier fight malignant

Language: Английский

Citations

22

The Web-Based Portal SpatialTME Integrates Histological Images with Single-Cell and Spatial Transcriptomics to Explore the Tumor Microenvironment DOI Open Access
Jintong Shi, Xia Wei, Zhenzhen Xun

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(8), P. 1210 - 1220

Published: Feb. 5, 2024

Abstract The tumor microenvironment (TME) represents a complex network in which cells communicate not only with each other but also stromal and immune cells. intercellular interactions the TME contribute to initiation, progression, metastasis, treatment outcome. Recent advances spatial transcriptomics (ST) have revolutionized molecular understanding of at level. A comprehensive interactive analysis resource specifically designed for characterizing could facilitate further using ST. In this study, we collected 296 ST slides covering 19 cancer types developed computational pipeline delineate structure along malignant–boundary–nonmalignant axis. identified differentially expressed genes their functional enrichment, deconvoluted cellular composition TME, reconstructed cell type–specific gene expression profiles sub-spot level, performed cell–cell interaction analysis. Finally, user-friendly database SpatialTME (http://www.spatialtme.yelab.site/) was constructed provide search, visualization, downloadable results. These detailed analyses are able reveal heterogeneous regulatory elucidate associations between features development or response therapy, offering valuable study TME. Significance: provides structure, composition, expression, function, information enable investigations into level advance treatment.

Language: Английский

Citations

19