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Cancer-associated fibroblasts (CAFs) are important, highly heterogeneous components of the tumor extracellular matrix that have different origins and express a diverse set of biomarkers. Different subtypes of CAFs participate in the immune regulation of the tumor microenvironment (TME). In addition to their role in supporting stromal cells, CAFs have multiple immunosuppressive functions, membrane and secretory patterns, against anti-tumor immunity. The inhibition of CAFs function and anti-TME therapy targeting CAFs provides new adjuvant means for immunotherapy. In this review, we outline the emerging understanding of CAFs with a particular emphasis on their origin and heterogeneity, different mechanisms of their regulation, as well as their direct or indirect effect on immune cells that leads to immunosuppression.
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http://dx.doi.org/10.3389/fimmu.2021.671595 | 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 PDFInt J Surg
September 2025
BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Thyroid cancer, a prevalent endocrine malignancy, is influenced by its tumor microenvironment (TME), with cancer-associated fibroblasts (CAFs) playing a pivotal role in disease progression. Molecularly, CAFs orchestrate a pro-tumorigenic niche via cytokine secretion and extracellular matrix (ECM) stiffening, underscoring their targetability. Therapeutic strategies, including small molecule inhibitor-based therapies, immune-based therapies, nanoparticle-based approaches, and combination regimens, have been evaluated for their efficacy in disrupting CAF functionality.
View Article and Find Full Text PDFOncol Res
September 2025
Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, 420008, Russia.
Melanoma is a malignant neoplasm with a high propensity to metastasize, arising from melanocytes and contributing significantly to global morbidity and mortality. Despite the demonstrated efficacy of many immunotherapy approaches, these methods rely on direct destruction of tumor cells with minimal impact on the aggregate of nearby non-tumor cells, the extracellular matrix, and blood vessels that form the tumor microenvironment (TME). The TME is known to be heterogeneous and dynamic, exerting both antitumor and pro-tumor effects depending on the specific features and stage of carcinogenesis.
View Article and Find Full Text PDFFront Immunol
September 2025
Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Intrinsic genetic alterations and dynamic transcriptional changes contribute to the heterogeneity of solid tumors. Lung adenocarcinoma (LUAD) is characterized by its significant histological, cellular and molecular heterogeneity. The present study aimed to study the spatial transcriptomics of primary LUAD with initial hopes to decipher molecular characteristics of subtype transitions in LUAD progression, offering new insights for novel therapeutic strategies.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
August 2025
Department of Neurology, The First Affiliated Hospital, Fujian Medical University, 350005 Fuzhou, Fujian, China.
Background: Glioblastoma (GBM) is an extremely aggressive brain tumor, marked by restricted therapeutic possibilities and a generally unfavorable prognosis. GBM's complexity and heterogeneity necessitate comprehensive genetic and immunological profiling to enhance therapeutic strategies.
Methods: The study integrated The Cancer Genome Atlas (TCGA) and Integrative Epidemiology Unit Open Genome-Wide Association Studies (IEU OpenGWAS) data to identify genetic factors influencing GBM using expression quantitative trait loci (eQTL) and genome-wide association studies (GWAS).