Reconstruction of the tumor spatial microenvironment along the malignant-boundary-nonmalignant axis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 20, 2023

Abstract Although advances in spatial transcriptomics (ST) enlarge to unveil landscape of tissues, it remains challenging delineate pathology-relevant and cellular localizations, interactions exclusive a niche (e.g., tumor boundary). Here, we develop Cottrazm, integrating ST with hematoxylin eosin histological image, single-cell the boundary connecting malignant non-malignant cell spots deconvolute cell-type composition at location, reconstruct type-specific gene expression profiles sub-spot level. We validate performance Cottrazm along malignant-boundary-nonmalignant axis. identify specific macrophage fibroblast subtypes localized around that interacted cells generate structural boundary, which limits T infiltration promotes immune exclusion microenvironment. In this work, provides an integrated tool framework dissect microenvironment facilitates discovery functional biological insights, thereby identifying therapeutic targets oncologic datasets.

Language: Английский

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Deep learning supported discovery of biomarkers for clinical prognosis of liver cancer

Nature Machine Intelligence, Journal Year: 2023, Volume and Issue: 5(4), P. 408 - 420

Published: April 3, 2023

Language: Английский

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Cold and hot tumors: from molecular mechanisms to targeted therapy

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

Published: Oct. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Language: Английский

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Presence of onco-fetal neighborhoods in hepatocellular carcinoma is associated with relapse and response to immunotherapy

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(1), P. 167 - 186

Published: Jan. 2, 2024

Language: Английский

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Advances in spatial transcriptomics and its applications in cancer research

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 20, 2024

Abstract Malignant tumors have increasing morbidity and high mortality, their occurrence development is a complicate process. The of sequencing technologies enabled us to gain better understanding the underlying genetic molecular mechanisms in tumors. In recent years, spatial transcriptomics been developed rapidly allow quantification illustration gene expression context tissues. Compared with traditional technologies, not only detect levels cells, but also inform location genes within tissues, cell composition biological interaction between cells. Here we summarize tools its application cancer research. We discuss limitations challenges current approaches, as well future prospects.

Language: Английский

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Spatial Transcriptomic and Metabolomic Landscapes of Oral Submucous Fibrosis‐Derived Oral Squamous Cell Carcinoma and its Tumor Microenvironment

Advanced Science, Journal Year: 2024, Volume and Issue: 11(12)

Published: Jan. 16, 2024

Abstract In South and Southeast Asia, the habit of chewing betel nuts is prevalent, which leads to oral submucous fibrosis (OSF). OSF a well‐established precancerous lesion, portion cases eventually progress squamous cell carcinoma (OSCC). However, specific molecular mechanisms underlying malignant transformation OSCC from are poorly understood. this study, leading‐edge techniques Spatial Transcriptomics (ST) Metabolomics (SM) integrated obtain spatial location information cancer cells, fibroblasts, immune as well transcriptomic metabolomic landscapes in OSF‐derived tissues. This work reveals for first time that some cells undergo partial epithelial–mesenchymal transition (pEMT) within situ (ISC) region, acquiring fibroblast‐like phenotypes participating collagen deposition. Complex interactions among epithelial tumor microenvironment demonstrated. Most importantly, significant metabolic reprogramming OSCC, including abnormal polyamine metabolism, potentially playing pivotal role promoting tumorigenesis evasion discovered. The ST SM data study shed new light on deciphering OSCC. also offers invaluable clues prevention treatment

Language: Английский

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METTL16 promotes liver cancer stem cell self-renewal via controlling ribosome biogenesis and mRNA translation

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Feb. 1, 2024

Abstract Background While liver cancer stem cells (CSCs) play a crucial role in hepatocellular carcinoma (HCC) initiation, progression, recurrence, and treatment resistance, the mechanism underlying CSC self-renewal remains elusive. We aim to characterize of Methyltransferase 16 (METTL16), recently identified RNA N 6 -methyladenosine (m A) methyltransferase, HCC development/maintenance, stemness, as well normal hepatogenesis. Methods Liver-specific Mettl16 conditional KO (cKO) mice were generated assess its pathogenesis Hydrodynamic tail-vein injection (HDTVi)-induced de novo hepatocarcinogenesis xenograft models utilized determine METTL16 initiation progression. A limiting dilution assay was evaluate frequency. Functionally essential targets revealed via integrative analysis multi-omics data, including RNA-seq, immunoprecipitation (RIP)-seq, ribosome profiling. Results is highly expressed CSCs depletion dramatically decreased frequency vitro vivo. significantly attenuated yet only slightly influenced Mechanistic studies, high-throughput sequencing, unveiled key regulator ribosomal (rRNA) maturation mRNA translation eukaryotic factor 3 subunit ( eIF3a ) transcript bona-fide target HCC. In addition, functionally regions by CRISPR gene tiling scan, which will pave way for development potential inhibitor(s). Conclusions Our findings highlight oncogenic promoting enhancing through augmenting efficiency.

Language: Английский

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Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment advanced HCC, but problems such as drug resistance immune-related adverse events still exist in clinical practice. immunosuppressive tumor microenvironment (TME) HCC restricts efficacy essential for progression metastasis. Therefore, it necessary to elucidate mechanisms behind TME develop apply immunotherapy. This review systematically summarizes pathogenesis formation TME, by which accelerates We also status further discuss existing challenges potential therapeutic strategies targeting TME. hope inspire optimizing innovating immunotherapeutic comprehensively understanding structure function HCC.

Language: Английский

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Decoder-seq enhances mRNA capture efficiency in spatial RNA sequencing

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 16, 2024

Language: Английский

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The Web-Based Portal SpatialTME Integrates Histological Images with Single-Cell and Spatial Transcriptomics to Explore the Tumor Microenvironment

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

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