Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Oct. 11, 2021

Abstract Cancer-associated fibroblasts (CAFs), a stromal cell population with cell-of-origin, phenotypic and functional heterogeneity, are the most essential components of tumor microenvironment (TME). Through multiple pathways, activated CAFs can promote growth, angiogenesis, invasion metastasis, along extracellular matrix (ECM) remodeling even chemoresistance. Numerous previous studies have confirmed critical role interaction between cells in tumorigenesis development. However, recently, mutual effects immune (TIME) been identified as another key factor promoting progression. The TIME mainly consists distinct populations islets is highly associated antitumor immunological state TME. interact tumor-infiltrating well other within via secretion various cytokines, growth factors, chemokines, exosomes effector molecules, consequently shaping an immunosuppressive TME that enables cancer to evade surveillance system. In-depth interactions, particularly complicated mechanisms connecting cells, might provide novel strategies for subsequent targeted immunotherapies. Herein, we shed light on recent advances regarding direct indirect crosstalk infiltrating further summarize possible immunoinhibitory induced by In addition, present current related CAF-targeting immunotherapies briefly describe some future perspectives CAF research end.

Language: Английский

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The Role of Fibroblast Growth Factor (FGF) Signaling in Tissue Repair and Regeneration

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 3242 - 3242

Published: Nov. 19, 2021

Fibroblast growth factors (FGFs) are a large family of secretory molecules that act through tyrosine kinase receptors known as FGF receptors. They play crucial roles in wide variety cellular functions, including cell proliferation, survival, metabolism, morphogenesis, and differentiation, well tissue repair regeneration. The signaling pathways regulated by FGFs include RAS/mitogen-activated protein (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)–protein B (AKT), phospholipase C gamma (PLCγ), signal transducer activator transcription (STAT). To date, 22 have been discovered, involved different functions the body. Several directly or indirectly interfere with during regeneration, addition to their critical maintenance pluripotency dedifferentiation stem cells. In this review, we summarize diverse processes shed light on importance mechanisms

Language: Английский

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Cancer-Associated Fibroblasts: Tumorigenicity and Targeting for Cancer Therapy

Cancers, Journal Year: 2022, Volume and Issue: 14(16), P. 3906 - 3906

Published: Aug. 12, 2022

Cancer-associated fibroblasts (CAFs) are a heterogenous group of activated and major component the tumor stroma. CAFs may be derived from fibroblasts, epithelial cells, endothelial cancer stem adipocytes, pericytes, or stellate cells. These complex origins underlie their functional diversity, which includes pro-tumorigenic roles in extracellular matrix remodeling, suppression anti-tumor immunity, resistance to therapy. Several methods for targeting inhibit progression enhance immunity have recently been reported. While preclinical studies shown promise, date they unsuccessful human clinical trials against melanoma, breast cancer, pancreas colorectal cancers. This review summarizes recent advances CAF-targeting therapies, including DNA-based vaccines, anti-CAF CAR-T modifying reprogramming CAF functions. The challenges developing effective treatment highlighted, include heterogeneity plasticity, lack specific target markers CAFs, limitations animal models recapitulating microenvironment, undesirable off-target systemic side effects. Overcoming these expanding our understanding basic biology is necessary making progress towards safe therapeutic strategies cancers patients.

Language: Английский

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Signaling pathways in cancer‐associated fibroblasts: recent advances and future perspectives

Cancer Communications, Journal Year: 2022, Volume and Issue: 43(1), P. 3 - 41

Published: Nov. 24, 2022

As a critical component of the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) play important roles in cancer initiation and progression. Well-known signaling pathways, including transforming growth factor-β (TGF-β), Hedgehog (Hh), Notch, Wnt, Hippo, nuclear factor kappa-B (NF-κB), Janus kinase (JAK)/signal transducer activator transcription (STAT), mitogen-activated protein (MAPK), phosphoinositide 3-kinase (PI3K)/AKT as well factors, hypoxia-inducible (HIF), heat shock 1 (HSF1), P53, Snail, Twist, constitute complex regulatory networks TME to modulate formation, activation, heterogeneity, metabolic characteristics malignant phenotype CAFs. Activated CAFs remodel influence biological processes cells by altering transcriptional secretory characteristics, this modulation partially depends on regulation cascades. The results preclinical clinical trials indicated that therapies targeting pathways demonstrated promising efficacy but were also accompanied some failures (e.g., NCT01130142 NCT01064622). Hence, comprehensive understanding cascades might help us better understand progression may facilitate development more efficient safer stroma-targeted therapies. Here, we review recent advances studies briefly discuss future perspectives CAF research.

Language: Английский

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Loss of cancer-associated fibroblast-derived exosomal DACT3-AS1 promotes malignant transformation and ferroptosis-mediated oxaliplatin resistance in gastric cancer

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 68, P. 100936 - 100936

Published: Jan. 31, 2023

Language: Английский

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3D bioprinted cancer models: from basic biology to drug development

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(12), P. 679 - 692

Published: Oct. 24, 2022

Language: Английский

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Heterogeneity of neuroendocrine transcriptional states in metastatic small cell lung cancers and patient-derived models

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 19, 2022

Abstract Molecular subtypes of small cell lung cancer (SCLC) defined by the expression key transcription regulators have recently been proposed in lines and limited number primary tumors. The clinical biological implications neuroendocrine (NE) metastatic SCLC, extent to which they vary within between patient tumors patient-derived models is not known. We integrate histology, transcriptome, exome, treatment outcomes SCLC from a range sites, revealing complex intra- intertumoral heterogeneity NE differentiation. Transcriptomic analysis confirms previously described based on ASCL1 , NEUROD1 POU2F3 YAP1 ATOH1 expression, reveal subtype with hybrid non-NE phenotypes, marked chemotherapy-resistance exceedingly poor outcomes. are more likely RB1 NOTCH chromatin modifier gene mutations, upregulation DNA damage response genes, respond replication stress targeted therapies. In contrast, patients preferentially benefited immunotherapy if their were non-NE. Transcriptional phenotypes strongly skew towards state model systems, an observation that was confirmed paired patient-matched xenografts. provide framework unifies transcriptomic genomic dimensions SCLC. differences transcriptional diversity systems development novel therapeutic agents.

Language: Английский

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Cancer-associated fibroblasts: The chief architect in the tumor microenvironment

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Jan. 30, 2023

Stromal heterogeneity of tumor microenvironment (TME) plays a crucial role in malignancy and therapeutic resistance. Cancer-associated fibroblasts (CAFs) are one the major players stroma. The heterogeneous sources origin subsequent impacts crosstalk with breast cancer cells flaunt serious challenges before current therapies to cure triple-negative (TNBC) other cancers. positive reciprocal feedback CAFs induce dictates their mutual synergy establishing malignancy. Their substantial creating tumor-promoting niche has reduced efficacy several anti-cancer treatments, including radiation, chemotherapy, immunotherapy, endocrine therapy. Over years, there been an emphasis on understanding CAF-induced resistance order enhance therapy results. CAFs, majority cases, employ crosstalk, stromal management, strategies generate resilience surrounding cells. This emphasizes significance developing novel that target particular CAF subpopulations, which will improve treatment sensitivity impede growth. In this review, we discuss progression, altering response agents cancer. addition, also potential possible approaches for CAF-mediated therapies.

Language: Английский

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Mechanisms of organ fibrosis: Emerging concepts and implications for novel treatment strategies

Molecular Aspects of Medicine, Journal Year: 2023, Volume and Issue: 92, P. 101191 - 101191

Published: May 24, 2023

Language: Английский

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Emerging histopathological parameters in the prognosis of oral squamous cell carcinomas.

PubMed, Journal Year: 2024, Volume and Issue: 39(1), P. 1 - 12

Published: Jan. 1, 2024

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy, representing 90% of all malignant neoplasms in head and neck region. Patients with this aggressive tumor have an overall 5-year survival rate approximately 50%, which drops to less than 30% when tumors are diagnosed at advanced clinical stages. Over decades, several studies provided high-level evidence impact histopathological features on treatment guidelines prognosis OSCC. The 8th American Joint Committee Cancer (AJCC) TNM staging system recognized importance depth invasion T category extranodal extension N for This review provides current knowledge emerging parameters identified as potential biomarkers OSCC, such invasion, thickness, pattern inflammatory profile, tumor-stroma ratio, evaluating their relevance patient outcomes. Analysis, limitations, biological mechanisms highlighted discussed. Assessing reporting these markers cost-effective can be incorporated into daily practice.

Language: Английский

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