Nanomaterials in cancer immunotherapy: targeting cancer-associated fibroblasts

Cancer Nanotechnology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 17, 2025

Emphasizing the significance of cancer-associated fibroblasts (CAFs), non-malignant yet pivotal players within tumor microenvironment (TME), this review illuminates role inflammatory subtype (iCAF) as catalysts in cancer proliferation, metastasis, and therapeutic resistance. Given their paramount importance, targeting CAFs emerges a robust strategy evolving landscape immunotherapy. Nanomaterials, distinguished by unique features malleability, hold considerable promise biomedicine, especially precision-oriented domain therapy. Their aptitude for modulating immune responses, amplifying drug efficacy through precise delivery, discerningly focusing on cells TME situates nanomaterials formidable tools to transcend boundaries set conventional treatments. This scrutinizes convoluted interplay among CAFs, cells, TME. It further showcases widely utilized management. We underscore potential nanoscale delivery systems directed at underscoring transformative power revolutionizing therapies, enhancing precision, culminating improved patient outcomes.

Language: Английский

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Chemoresistance and the tumor microenvironment: the critical role of cell–cell communication

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 10, 2024

Resistance of cancer cells to anticancer drugs remains a major challenge in modern medicine. Understanding the mechanisms behind development chemoresistance is key developing appropriate therapies counteract it. Nowadays, with advances technology, we are paying more and attention role tumor microenvironment (TME) intercellular interactions this process. We also know that important elements TME not only themselves but other cell types, such as mesenchymal stem cells, cancer-associated fibroblasts, stromal macrophages. can communicate each indirectly (via cytokines, chemokines, growth factors, extracellular vesicles [EVs]) directly gap junctions, ligand-receptor pairs, adhesion, tunnel nanotubes). This communication appears be critical for chemoresistance. EVs seem particularly interesting structures regard. Within these structures, lipids, proteins, nucleic acids transported, acting signaling molecules interact numerous biochemical pathways, thereby contributing Moreover, drug efflux pumps, which responsible removing from transported via EVs.

Language: Английский

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Integrative Single-Cell and Bulk RNA Sequencing Identifies a Macrophage-Related Prognostic Signature for Predicting Prognosis and Therapy Responses in Colorectal Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 811 - 811

Published: Jan. 19, 2025

Colorectal cancer (CRC) is one of the most common malignant tumors, characterized by a high incidence and mortality rate. Macrophages, as key immune cell type within tumor microenvironment (TME), play role in evasion progression CRC. Therefore, identifying macrophage biomarkers great significance for predicting prognosis CRC patients. This study integrates scRNA-seq bulk RNA-seq data to identify macrophage-related genes By applying comprehensive machine learning framework, prognostic signature (MRPS) was constructed 15 with values. The MRPS demonstrated strong predictive performance across multiple datasets, effectively stratifying high-risk low-risk patients terms overall survival (OS) disease-specific (DSS). Furthermore, analysis revealed significant differences between groups infiltration levels checkpoint gene expression patterns. Drug screening identified several small molecules, including Bortezomib Mitoxantrone, potential therapeutic options Pseudotime trajectory further highlighted comprising differentiation. provides powerful tool personalized prediction patients, offering new insights into macrophage-driven mechanisms strategies.

Language: Английский

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Exosomal SphK1 from colorectal cancer cells promotes cancer cell migration and activates hepatic stellate cells

Molecular Medicine Reports, Journal Year: 2025, Volume and Issue: 31(3)

Published: Jan. 23, 2025

Exosomes are small extracellular vesicles that naturally released into body fluids by cells. They rich in bioactive molecules such as proteins. Sphingosine kinase 1 (SphK1) is an important potential drug target for the treatment of cancer due to its functions regulate cell migration, growth, apoptosis and angiogenesis. Tumor exosomes abundantly surround primary tumors, exchanging transferring information between cells modulating progression. Given importance exosomes, involvement exosomal SphK1 from colorectal (CRC) migration these activation hepatic stellate was investigated. Firstly, plasma protein expression, tested ELISA, compared patients with CRC without metastasis those liver metastasis. The results revealed levels were significantly upregulated CRC. Secondly, different expression SphK1, which regulated transfection, isolated evaluate their effect on E‑cadherin vimentin cells, assessed western blotting. demonstrated depletion partially reversed exosome‑induced caused decreased increased levels. Thirdly, effects investigated, α‑SMA, TNF‑α TGF‑β blotting LX‑2 Moreover, AKT phosphorylated (p‑)AKT also activated upregulating p‑AKT, this effect. Furthermore, application agonist inhibition activation, induced SphK1. Finally, investigation viability, analyzed CCK‑8 assay, assessment PCNA a proliferation marker, blot, culture supernatant promoted viability Overall, regulating p‑AKT. This suggests may serve key role potentially

Language: Английский

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CircRNAs in Colorectal Cancer: Unveiling Their Roles and Exploring Therapeutic Potential

Biochemical Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Language: Английский

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Spatial and single‐cell transcriptomic analysis reveals fibroblasts dependent immune environment in colorectal cancer

BioFactors, Journal Year: 2025, Volume and Issue: 51(2)

Published: March 1, 2025

Abstract Colorectal cancer (CRC) exhibits a complex tumor microenvironment with significant cellular heterogeneity, particularly involving cancer‐associated fibroblasts that influence behavior and metastasis. This study integrated single‐cell RNA sequencing spatial transcriptomics to dissect fibroblast heterogeneity in CRC. Data processing employed Seurat for quality control, principal component analysis dimensionality reduction, t‐Distributed Stochastic Neighbor Embedding visualization. Differentially expressed genes were identified using DESeq2. Immune infiltration was assessed via Single‐Sample Gene Set Enrichment Analysis, CIBERSORT, xCell algorithms. Prognostic through univariate Cox regression, followed by consensus clustering survival analysis. Metabolic pathways explored scMetabolism. Experimental validation involved CCK8, scratch, Transwell assays evaluate the roles of key BGN CERCAM CRC cell proliferation Machine learning‐driven four fibroblast‐associated (TRIP6, TIMP1, BGN, CERCAM) demonstrating prognostic relevance Consensus based on these biomarkers stratified patients into three distinct molecular subtypes (Clusters A–C). Notably, Cluster C exhibited most unfavorable clinical outcomes coupled marked upregulation all fibroblast‐related genes. Comprehensive immune profiling revealed paradoxical features C: heightened global activation (characterized substantial leukocyte infiltration) coexisted specific immunosuppressive elements, including enrichment pro‐tumorigenic M0 macrophages, depletion anti‐tumor plasma cells, resting memory CD4+ T along coordinated multiple checkpoint molecules. Computational prediction TIDE platform suggested enhanced immunotherapy responsiveness patients. Functional demonstrated knockdown or significantly impaired malignant phenotypes, reducing proliferative capacity, migration potential, invasive ability. Fibroblasts demonstrate within microenvironment, impacting prognosis therapeutic responses. Key emerge as potential immunotherapeutic targets, offering new strategies precision treatment

Language: Английский

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Exploring the Role of Cellular Interactions in the Colorectal Cancer Microenvironment

Journal of Immunology Research, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Colorectal cancer (CRC) stands as one of the tumors with globally high incidence and mortality rates. In recent years, researchers have extensively explored role tumor immune microenvironment (TME) in CRC, highlighting crucial influence cell populations driving progression shaping therapeutic outcomes. The TME encompasses an array cellular noncellular constituents, spanning cells, myeloid tumor-associated fibroblasts, among others. However, composition within is highly dynamic, evolving throughout different stages progression. These shifts subpopulation proportions lead to a gradual transition response, shifting from early antitumor growth late-stage environment that supports survival. Therefore, it further investigate understand complex interactions various TME. this review, we explore key components varying origins, subpopulations shared elements CRC TME, examining their interconnections critical considerations for developing personalized precise immunotherapy strategies.

Language: Английский

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Integrative analysis of anoikis-related genes prognostic signature with immunotherapy and identification of CDKN3 as a key oncogene in lung adenocarcinoma

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113282 - 113282

Published: Oct. 8, 2024

Language: Английский

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