Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

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

Published: Oct. 2, 2023

Abstract Despite centuries since the discovery and study of cancer, cancer is still a lethal intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as pivotal component tumor microenvironment. The versatility sophisticated mechanisms CAFs in facilitating progression been elucidated extensively, including promoting angiogenesis metastasis, inducing drug resistance, reshaping extracellular matrix, developing an immunosuppressive Owing to their robust tumor-promoting function, are considered promising target for oncotherapy. However, highly heterogeneous group cells. Some subpopulations exert inhibitory role growth, which implies that CAF-targeting approaches must be more precise individualized. This review comprehensively summarize origin, phenotypical, functional heterogeneity CAFs. More importantly, we underscore advances strategies clinical trials CAF various cancers, also progressions immunotherapy.

Language: Английский

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Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and Cholangiocarcinoma

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2023, Volume and Issue: 15(4), P. 985 - 999

Published: Jan. 1, 2023

Primary liver cancer (PLC) includes hepatocellular carcinoma and intrahepatic cholangiocarcinoma is the sixth most common worldwide with poor prognosis. PLC characterized by an abundant stromal reaction in which cancer-associated fibroblasts (CAFs) are one of major components. Solid evidence has demonstrated crucial role CAFs tumor progression, CAF abundance often correlated clinical outcomes. Although regarded as attractive promising target for treatment, a understanding origins heterogeneity lack specific markers hurdles to efficient CAF-specific therapy. In this review, we examine recent advances diversity context biomarkers, subtypes, functions PLC. The regulatory roles extracellular matrix remodeling, metastasis, stemness, therapeutic resistance summarized. With increasing link between reduced antitumor immune responses, provide updated knowledge on crosstalk cells within microenvironment, leads resistance. addition, present current CAF-targeted therapies describe some future perspectives. A better biology will shed light novel strategy against

Language: Английский

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Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives

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

Published: Aug. 2, 2024

Abstract Metastasis remains a pivotal characteristic of cancer and is the primary contributor to cancer-associated mortality. Despite its significance, mechanisms governing metastasis are not fully elucidated. Contemporary findings in domain biology have shed light on molecular aspects this intricate process. Tumor cells undergoing invasion engage with other cellular entities proteins en route their destination. Insights into these engagements enhanced our comprehension principles directing movement adaptability metastatic cells. The tumor microenvironment plays role facilitating proliferation by enabling navigate through stromal barriers. Such attributes influenced genetic epigenetic changes occurring surrounding milieu. A profound understanding process’s biological indispensable for devising efficacious therapeutic strategies. This review delves recent developments concerning metastasis-associated genes, important signaling pathways, microenvironment, metabolic processes, peripheral immunity, mechanical forces metastasis. In addition, we combine advances particular emphasis prospect developing effective interventions including most popular immunotherapies nanotechnology combat We also identified limitations current research metastasis, encompassing drug resistance, restricted animal models, inadequate biomarkers early detection methods, as well heterogeneity among others. It anticipated that comprehensive will significantly contribute advancement research.

Language: Английский

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Cancer-associated fibroblasts: a versatile mediator in tumor progression, metastasis, and targeted therapy

Cancer and Metastasis Reviews, Journal Year: 2024, Volume and Issue: 43(3), P. 1095 - 1116

Published: April 11, 2024

Abstract Tumor microenvironment (TME) has been demonstrated to play a significant role in tumor initiation, progression, and metastasis. Cancer-associated fibroblasts (CAFs) are the major component of TME exhibit heterogeneous properties their communication with cells. This heterogeneity CAFs can be attributed various origins, including quiescent fibroblasts, mesenchymal stem cells (MSCs), adipocytes, pericytes, endothelial cells, mesothelial Moreover, single-cell RNA sequencing identified diverse phenotypes CAFs, myofibroblastic (myCAFs) inflammatory (iCAFs) being most acknowledged, alongside newly discovered subtypes like antigen-presenting (apCAFs). Due these heterogeneities, exert multiple functions tumorigenesis, cancer stemness, angiogenesis, immunosuppression, metabolism, As result, targeted therapies aimed at TME, particularly focusing on rapidly developing, fueling promising future advanced tumor-targeted therapy.

Language: Английский

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A Molecular Perspective on HIF-1α and Angiogenic Stimulator Networks and Their Role in Solid Tumors: An Update

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3313 - 3313

Published: March 14, 2024

Hypoxia-inducible factor-1α (HIF-1α) is a major transcriptional factor, which plays an important role in cellular reprogramming processes under hypoxic conditions, facilitate solid tumors' progression. HIF-1α directly involved the regulation of angiogenesis, metabolic reprogramming, and extracellular matrix remodeling tumor microenvironment. Therefore, in-depth study on malignancies required to develop novel anti-cancer therapeutics. also critical regulating growth factors, such as vascular endothelial fibroblast platelet-derived network manner. Additionally, it significant progression chemotherapy resistance by variety angiogenic including angiopoietin 1 2, metalloproteinase, erythropoietin, along with energy pathways. this review attempts provide comprehensive insight into angiogenesis pathways tumors.

Language: Английский

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Distinct fibroblast subpopulations associated with bone, brain or intrapulmonary metastasis in advanced non‐small‐cell lung cancer

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(3)

Published: March 1, 2024

Abstract Background Bone or brain metastases may develop in 20–40% of individuals with late‐stage non‐small‐cell lung cancer (NSCLC), resulting a median overall survival only 4–6 months. However, the primary tissue's distinctions between bone, and intrapulmonary NSCLC at single‐cell level have not been underexplored. Methods We conducted comprehensive analysis 14 tissue biopsy samples obtained from treatment‐naïve advanced patients bone ( n = 4), 6) 4) metastasis using sequencing originating lungs. Following quality control removal doublets, total 80 084 cells were successfully captured. Results The most significant inter‐group differences observed fraction function fibroblasts. identified three distinct cancer‐associated fibroblast (CAF) subpopulations: myofibroblastic CAF (myCAF), inflammatory (iCAF) antigen‐presenting (apCAF). Notably, apCAF was prevalent metastasis, while iCAF dominated metastasis. Intercellular signalling network revealed that play role by activating pathways associated stemness, such as SPP1‐CD44 SPP1‐PTGER4. Conversely, found to promote invasion metastasis‐related molecules, MET hepatocyte growth factor. Furthermore, interaction CAFs tumour influenced T‐cell exhaustion within microenvironment. Conclusions This study unveils direct interplay identifies potential therapeutic targets for inhibiting disrupting these critical cell–cell interactions.

Language: Английский

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Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: Jan. 9, 2025

Abstract Research into cancer treatment has been mainly focused on developing therapies to directly target cells. Over the past decade, extensive studies have revealed critical roles of tumour microenvironment (TME) in initiation, progression, and drug resistance. Notably, cancer-associated fibroblasts (CAFs) emerged as one primary contributors shaping TME, creating a favourable environment for development. Many preclinical identified promising targets CAFs, demonstrating remarkable efficacy some CAF-targeted treatments models. Encouraged by these compelling findings, therapeutic strategies now advanced clinical evaluation. We aim provide comprehensive review relevant subjects including CAF-related markers targets, their multifaceted roles, current landscape ongoing trials. This knowledge can guide future research CAFs advocate investigations targeting CAFs.

Language: Английский

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Immune System and Hepatocellular Carcinoma (HCC): New Insights into HCC Progression

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11471 - 11471

Published: July 14, 2023

According to the WHO's recently released worldwide cancer data for 2020, liver ranks sixth in morbidity and third mortality among all malignancies. Hepatocellular carcinoma (HCC), most common kind of cancer, accounts approximately 80% primary malignancies is one leading causes death globally. The intractable tumor microenvironment plays an important role development progression HCC three major unresolved issues clinical practice (cancer recurrence, fatal metastasis, refractory microenvironment). Despite significant advances, improved molecular cellular characterization still required since it genesis HCC. purpose this review present overview immune microenvironment, distinct constituents, current therapies, potential immunotherapy methods.

Language: Английский

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Emerging Role of Cancer-Associated Fibroblasts in Progression and Treatment of Hepatocellular Carcinoma

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3941 - 3941

Published: Feb. 15, 2023

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and fourth leading cause cancer-related death globally. Tumor cells recruit remodel various types stromal inflammatory to form a tumor microenvironment (TME), which encompasses cellular molecular entities, including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), neutrophils (TANs), immune cells, myeloid-derived suppressor (MDSCs), checkpoint molecules cytokines that promote cancer cell growth, as well their drug resistance. HCC usually arises in context cirrhosis, always associated with an enrichment activated are owed chronic inflammation. CAFs major component TME, providing physical support it secreting proteins, such extracellular matrices (ECMs), hepatocyte growth factor (HGF), insulin-like 1/2 (ILGF1/2) can modulate survival. As such, CAF-derived signaling may increase pool resistant thus reducing duration clinical responses increasing degree heterogeneity within tumors. Although often implicated be metastasis resistance, several studies have reported significant phenotypic functional heterogeneity, some display antitumor drug-sensitizing properties. Multiple highlighted relevance crosstalk between other influence progression. basic partially revealed emerging roles immunotherapy resistance evasion, better understanding unique functions progression will contribute development more effective molecular-targeted drugs. In this review article, mechanisms involved CAFs, effects on HCC-cell metastasis, outcomes, comprehensively discussed.

Language: Английский

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TGF-β1 dominates stromal fibroblast-mediated EMT via the FAP/VCAN axis in bladder cancer cells

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 17, 2023

Bladder cancer is one of the most common malignant tumors urinary system and associated with a poor prognosis once invasion distant metastases occur. Epithelial-mesenchymal transition (EMT) drives metastasis in bladder cancer. Transforming growth factor β1 (TGF-β1) stromal fibroblasts, especially cancer-associated fibroblasts (CAFs), are positive regulators EMT However, it remains unclear how TGF-β1 mediates crosstalk between cells CAFs induces fibroblast-mediated We aimed to investigate mechanism regulation cells. Primary high expression fibroblast activation protein (FAP) were isolated from tissue samples. Subsequently, different conditioned media used stimulate cell line T24 co-culture system. Gene set enrichment analysis, human cytokine antibody array, cytological assays performed Among TGF-β family, was highly expressed primary supernatant. In tumor microenvironment, mainly derived CAFs. stimulated cells, fibroblast-derived promoted migration, invasion, EMT. Furthermore, inducing CAF-like features, by upregulating FAP normal line. Stromal induced TGF-β1/FAP. Versican (VCAN), downstream molecule FAP, plays an essential role TGF-β1/FAP axis-induced VCAN may also function through PI3K/AKT1 signaling pathway. critical mediator revealed new whereby dominated via FAP/VCAN axis identified potential biomarkers (FAP, VCAN, N-cadherin, Vimentin) These results enhance our understanding provide strategies for diagnosis, treatment, prognosis.

Language: Английский

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