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Cancer-associated fibroblasts (CAFs) are pivotal in shaping the immunosuppressive and chemoresistant tumor microenvironment (TME) of osteosarcoma (OS). This review explores how CAFs drive OS progression through paracrine signaling (e.g., TGF-β, IL-6), extracellular matrix (ECM) remodeling, exosome-mediated crosstalk, and metabolic reprogramming. We highlight CAF heterogeneity (e.g., myCAFs, iCAFs) and their roles in therapy resistance, emphasizing emerging strategies such as FAP inhibitors, TGF-β blockers, and CXCR4 antagonists. Combining these approaches with immunotherapy or chemotherapy offers promise for overcoming chemoresistance. Challenges like CAF plasticity and biomarker development are discussed, alongside future directions for precision targeting in OS.
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http://dx.doi.org/10.3389/fimmu.2025.1621521 | DOI Listing |
Mol Biol Rep
September 2025
Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
Background: Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. The tumor microenvironment (TME), particularly the interactions between endothelial cells and cancer-associated fibroblasts (CAFs), plays a pivotal role in promoting tumor growth, angiogenesis, oxidative stress, and therapy resistance. The HUVEC-fibroblast co-culture model closely mimics stromal-endothelial interactions observed in CRC, enabling mechanistic insights not achievable in monocultures.
View Article and Find Full Text PDFCancer Biol Med
September 2025
Department of Urology, First Affiliated Hospital of Jiujiang Medical University, Jiujiang 332000, China.
Prostate cancer is a significant global health issue with inflammation emerging as a critical driver of progression. The prostate tumor microenvironment (TME) is comprised of tumor cells, mesenchymal stem cells, immune cells, cancer-associated fibroblasts, adipocytes, and the extracellular matrix. All of these TME components interact soluble factors, such as growth factors, cytokines, and chemokines.
View Article and Find Full Text PDFBiochim Biophys Acta Rev Cancer
September 2025
Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha 410008, Hunan, China; Hunan Key Laboratory of Oral Health Research & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Hunan 3D Printing Engineering Research Center of Oral Care
Innate immune cells play an important role in the immune system and are mainly responsible for the rapid response to foreign pathogens, damaged tissues, or abnormal cells. However, their immunophenotype in oral squamous cell carcinoma (OSCC) is altered due to the influence of various components within the tumour microenvironment, including tumour cells, cancer associated fibroblasts, and the extracellular matrix. This immunophenotypic shift results in the suppression of anti-tumour-related immune functions and active participation in further remodelling of the tumour microenvironment.
View Article and Find Full Text PDFJ Control Release
September 2025
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Lane. 833 Zhizaoju Road, Shanghai 200011, China; Department of Biomedical Engineerin
Radiotherapy (RT) is a mainstay of cancer treatment but is limited by tumor resistance and off-target tissue damage, often mediated by therapy-induced cellular senescence. Here, we developed a "one-two punch" nanodrug, Lipo@ABT263@Au, that integrated a senolytic agent (ABT-263) with a gold-shelled liposome for radiosensitization and sustained drug release. High-throughput screening and transcriptomic analysis identified senescence as a key RT-induced vulnerability.
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
September 2025
Univ. of Pennsylvania, Medicine, Philadelphia, Pennsylvania, United States.
Lymphangioleiomyomatosis (LAM) is a rare lung disease caused by hyperactivation of the mechanistic/mammalian target of rapamycin 1 (mTORC1) growth pathway in a subset of mesenchymal lung cells. Histopathologically, LAM lesions have been described as immature smooth muscle-like cells positive for the immature melanocytic marker HMB45/PMEL/gp100 and phosphorylated ribosomal protein S6 (pS6). Advances in single cell sequencing (scRNA-seq) technology allowed us to group LAM cells according to their expression of cancer stem cell (CSC) genes and identify three clusters: a high CSC-like state (SLS), an intermediate state, and a low CSC-like inflammatory state (IS).
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