Pan-cancer spatially resolved single-cell analysis reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 13, 2023

Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population that plays crucial role in remodeling the tumor microenvironment (TME). Here, through integrated analysis of spatial and single-cell transcriptomics data across six common cancer types, we identified four distinct functional subgroups CAFs described their distribution characteristics. Additionally, RNA sequencing (scRNA-seq) from three additional types two newly generated scRNA-seq datasets rare namely epithelial-myoepithelial carcinoma (EMC) mucoepidermoid (MEC), expanded our understanding CAF heterogeneity. Cell-cell interaction conducted within context highlighted pivotal roles matrix (mCAFs) angiogenesis inflammatory (iCAFs) shaping immunosuppressive microenvironment. In patients with breast (BRCA) undergoing anti-PD-1 immunotherapy, iCAFs demonstrated heightened capacity facilitating proliferation, promoting epithelial-mesenchymal transition (EMT), contributing to establishment an Furthermore, scoring system based on showed significant correlation immune therapy response melanoma patients. Lastly, provided web interface ( https://chenxisd.shinyapps.io/pancaf/ ) for research community investigate pan-cancer.

Language: Английский

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Immunomodulatory biomaterials against bacterial infections: Progress, challenges, and future perspectives

The Innovation, Journal Year: 2023, Volume and Issue: 4(6), P. 100503 - 100503

Published: Aug. 29, 2023

•Insights into the intricate facets of immune microenvironment hold key to pioneering clinical strategies in combatting bacterial infections.•The design principles for antimicrobial biomaterials vary depending on at different stages infection.•Immunomodulatory display robust efficacy and vaccine attributes animals trials, promising intractable infections. Bacterial infectious diseases are one leading causes death worldwide. Even with use multiple antibiotic treatment strategies, 4.95 million people died from drug-resistant infections 2019. By 2050, number deaths will reach 10 annually. The increasing mortality may be partly due heterogeneity infection microenvironment, such as bacteria, biofilms, persister cells, intracellular small colony variants. In addition, complexity makes direct activity unsatisfactory long-term chronic attributed failing modulate active action cells. Therefore, there is an urgent need effective alternatives treat Accordingly, development immunomodulatory has recently received considerable interest; however, a comprehensive review their research progress lacking. this review, we focus mainly future perspectives used infection. First, describe characteristics acute phases Then, highlight corresponding advantages disadvantages. Moreover, discuss biomaterial-mediated vaccines' potential applications challenges activating innate adaptive memory. This serve reference studies develop next-generation accelerate translation practice.

Language: Английский

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Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma therapy: Challenges and opportunities

Cancer Letters, Journal Year: 2024, Volume and Issue: 591, P. 216859 - 216859

Published: April 13, 2024

Pancreatic ductal adenocarcinoma (PDAC) is a solid organ malignancy with high mortality rate. Statistics indicate that its incidence has been increasing as well the associated deaths. Most patients PDAC show poor response to therapies making clinical management of this cancer difficult. Stromal cells in tumor microenvironment (TME) contribute development resistance therapy cells. Cancer-associated fibroblasts (CAFs), most prevalent stromal TME, promote desmoplastic response, produce extracellular matrix proteins and cytokines, directly influence biological behavior These multifaceted effects make it difficult eradicate from body. As result, CAF-targeting synergistic therapeutic strategies have gained attention recent years. However, due substantial heterogeneity CAF origin, definition, function, plasticity, majority available approaches are not effective, some cases, they exacerbate disease progression. This review primarily elucidates on effect CAFs efficiency various treatment modalities, including chemotherapy, radiotherapy, immunotherapy, targeted therapy. Strategies for targeting also discussed.

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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Integrating single-cell and bulk RNA sequencing data unveils antigen presentation and process-related CAFS and establishes a predictive signature in prostate cancer

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 14, 2024

Abstract Background Cancer-associated fibroblasts (CAFs) are heterogeneous and can influence the progression of prostate cancer in multiple ways; however, their capacity to present process antigens PRAD has not been investigated. In this study, antigen presentation process-related CAFs (APPCAFs) were identified using bioinformatics, clinical implications APPCAF-related signatures Methods SMART technology was used sequence transcriptome primary isolated from patients undergoing different treatments. Differential expression gene (DEG) screening conducted. A CD4 + T-cell early activation assay assess degree T cells. The datasets obtained Cancer Genome Atlas (TCGA) database NCBI Gene Expression Omnibus (GEO), list 431 genes InnateDB database. Subsequently, APP-related by nonnegative matrix factorization (NMF) based on a single-cell seq (scRNA) matrix. GSVA functional enrichment analyses performed depict biological functions. risk signature (APPCAFRS) developed least absolute shrinkage selection operator (LASSO) regression analysis, independence score as prognostic factor evaluated univariate multivariate Cox analyses. Furthermore, biochemical recurrence-free survival (BCRFS)-related nomogram established, immune-related characteristics assessed ssGSEA function. immune treatment response further analyzed Tumor Immune Dysfunction Exclusion (TIDE) tool. levels hub APPCAFRS verified cell models. Results There 134 upregulated 147 downregulated genes, totaling 281 differentially expressed among CAFs. functions pathways DEGs significantly enriched processing processes, MHC class II protein complex transport vesicle, binding, intestinal network for IgA production. Androgen withdrawal diminished effect NMF clustering APPRGs, pseudotime analysis yielded CAF subtype CTSK MRC2 CAF-C1. CAF-C1 cells exhibited ligand‒receptor connections with epithelial Additionally, we found strong association between inflammatory Through differential NoneAPP-CAF-C2 subgroups, 55 significant identified, namely, APPCAFRGs. Based profiles APPCAFRGs, divided TCGA-PRAD cohort into two clusters consistent cluster genetic coefficient serving evaluation index. Four THBS2, DPT, COL5A1, MARCKS, develop capable predicting BCR occurrence patients. stability accuracy constructed Gleason grade (p = n.s.), PSA < 0.001), stage 0.05), 0.01). infiltration showed positive correlation abundance resting memory cells, M1 macrophages, dendritic score. addition, mRNA MARCKS models results bioinformatics analysis. Conclusions four potential APPCAFRGs developed, interaction microenvironment may play crucial role castration resistance PRAD. This novel approach provides valuable insights pathogenesis offers unexplored targets future research.

Language: Английский

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CAF-induced physical constraints controlling T cell state and localization in solid tumours

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(10), P. 676 - 693

Published: Sept. 9, 2024

Language: Английский

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Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

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Training and experimental validation a novel anoikis- and epithelial‒mesenchymal transition-related signature for evaluating prognosis and predicting immunotherapy efficacy in gastric cancer

Journal of Cancer, Journal Year: 2025, Volume and Issue: 16(4), P. 1078 - 1100

Published: Jan. 6, 2025

Anoikis resistance and improper activation of epithelial‒mesenchymal transition (EMT) are critical factors in tumor metastasis progression. Despite their interaction, the combined impact anoikis EMT on prognosis immunotherapy gastric cancer remains underexplored. In this study, we identified 354 anoikis- EMT-related genes (AERGs) through Venn analysis performed unsupervised clustering to classify patients into two molecular clusters: A B. Molecular cluster showed poor an immunosuppressive microenvironment, suggesting a "cold tumor" phenotype. Then, novel AERG-related prognostic model comprising CD24, CRYAB, MMP11, MUC4, PRKAA2, SERPINE1, SKP2, TP53 was constructed validated, accurately predicting 1-, 3-, 5-year survival rates patients. Multivariate revealed that risk score independent factor (hazard ratio = 1.651, 95% confidence interval 1.429-1.907, P<0.001). Further studies demonstrated that, compared high-risk group, low-risk group exhibited higher CD8+ T cell infiltration, mutational burden, immunophenoscores, lower immune dysfunction exclusion scores, indicating potential sensitivity immunotherapy. RT‒qPCR immunohistochemical staining validated expression levels model's markers. Overall, our shows promise for outcomes guiding selection tailored precise therapies

Language: Английский

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Drug Delivery System Targeting Cancer-Associated Fibroblast for Improving Immunotherapy

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 483 - 503

Published: Jan. 1, 2025

Abstract: Cancer-associated fibroblasts (CAFs) are a heterogeneous population of non-malignant cells that play crucial role in the tumor microenvironment, increasingly recognized as key contributors to cancer progression, metastasis, and treatment resistance. So, targeting CAFs has always been considered an important part immunotherapy. However, improve efficacy therapy is currently major challenge. Nanomaterials show their unique advantages whole process. At present, nanomaterials have achieved significant accomplishments medical applications, particularly field cancer-targeted therapy, showing enormous potential. It confirmed can not only directly target CAFs, but also interact with microenvironment (TME) immune affect tumorigenesis. As for treatment, could enhance therapeutic effect many ways. Therefore, this review, we first summarized current understanding complex interactions between TME, cells, cells. Next, discussed common modern medicine respective impacts on tumors. Finally, focus application nano drug delivery system therapy. Keywords: cancer-associated fibroblasts, delivery, nanomedicine, immunotherapy

Language: Английский

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Prognostic implications and therapeutic opportunities related to CAF subtypes in CMS4 colorectal cancer: insights from single-cell and bulk transcriptomics

APOPTOSIS, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Language: Английский

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