Role of cancer‐associated fibroblast subpopulations in immune infiltration, as a new means of treatment in cancer

Immunological Reviews, Journal Year: 2021, Volume and Issue: 302(1), P. 259 - 272

Published: May 19, 2021

Abstract The tumor microenvironment (TME) has been identified as one of the driving factors progression and invasion. Within this microenvironment, cancer‐associated fibroblasts (CAF) have multiple tumor‐promoting functions play key roles in drug resistance, through mechanisms, including extracellular matrix (ECM) remodeling, production growth factors, cytokines, chemokines, modulation metabolism angiogenesis. More recently, a growing body evidence shown that CAF also modulate immune cell activity suppress anti‐tumor response. In review, we describe current knowledge on heterogeneity terms identity functions. Moreover, analyze how distinct subpopulations differentially interact with cells, particular focus T lymphocytes. We address specific subsets contribute to cancer induction an immunosuppressive microenvironment. Finally, highlight potential therapeutic strategies for targeting cancer.

Language: Английский

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Targeting the tumor stroma for cancer therapy

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Nov. 2, 2022

Tumors are comprised of both cancer cells and surrounding stromal components. As an essential part the tumor microenvironment, stroma is highly dynamic, heterogeneous commonly tumor-type specific, it mainly includes noncellular compositions such as extracellular matrix unique cancer-associated vascular system well a wide variety cellular components including activated fibroblasts, mesenchymal cells, pericytes. All these elements operate with each other in coordinated fashion collectively promote initiation, progression, metastasis therapeutic resistance. Over past few decades, numerous studies have been conducted to study interaction crosstalk between neoplastic cells. Meanwhile, we also witnessed exponential increase investigation recognition critical roles solid tumors. A series clinical trials targeting launched continually. In this review, introduce discuss current advances understanding various their cancers. We elaborate on potential novel approaches for tumor-stroma-based targeting, aim leap from bench bedside.

Language: Английский

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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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Tumor microenvironment signaling and therapeutics in cancer progression

Cancer Communications, Journal Year: 2023, Volume and Issue: 43(5), P. 525 - 561

Published: April 2, 2023

Abstract Tumor development and metastasis are facilitated by the complex interactions between cancer cells their microenvironment, which comprises stromal extracellular matrix (ECM) components, among other factors. Stromal can adopt new phenotypes to promote tumor cell invasion. A deep understanding of signaling pathways involved in cell‐to‐cell cell‐to‐ECM is needed design effective intervention strategies that might interrupt these interactions. In this review, we describe microenvironment (TME) components associated therapeutics. We discuss clinical advances prevalent newly discovered TME, immune checkpoints immunosuppressive chemokines, currently used inhibitors targeting pathways. These include both intrinsic non‐autonomous TME: protein kinase C (PKC) signaling, Notch, transforming growth factor (TGF‐β) Endoplasmic Reticulum (ER) stress response, lactate Metabolic reprogramming, cyclic GMP–AMP synthase (cGAS)–stimulator interferon genes (STING) Siglec also recent Programmed Cell Death Protein 1 (PD‐1), Cytotoxic T‐Lymphocyte Associated 4 (CTLA4), T‐cell immunoglobulin mucin‐3 (TIM‐3) Lymphocyte Activating Gene 3 (LAG3) checkpoint along with C‐C chemokine receptor (CCR4)‐ class chemokines 22 (CCL22)/ 17 (CCL17), type 2 (CCR2)‐ (C‐C motif) ligand (CCL2), 5 (CCR5)‐ (CCL3) axis TME. addition, review provides a holistic TME as three‐dimensional microfluidic models believed recapitulate original characteristics patient hence may be platform study mechanisms screen for various anti‐cancer therapies. further systemic influences gut microbiota reprogramming treatment response. Overall, comprehensive analysis diverse most critical highlighting newest preclinical studies underlying biology. highlight importance technologies microfluidics lab‐on‐chip research present an overview extrinsic factors, such inhabitant human microbiome, have potential modulate biology drug responses.

Language: Английский

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Cancer-associated fibroblasts and resistance to anticancer therapies: status, mechanisms, and countermeasures

Cancer Cell International, Journal Year: 2022, Volume and Issue: 22(1)

Published: April 29, 2022

Cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment (TME) with diverse functions such as extracellular matrix (ECM) remodeling, modulation metabolism and angiogenesis, crosstalk both cancer cells infiltrating immune by production growth factors, cytokines, chemokines. Within TME milieu, CAFs exhibit morphological functional transitions relatively specific markers hold tremendous potential to facilitate tumorigenesis, development, resistance towards multiple therapeutic strategies including chemotherapy, radiotherapy, targeted therapy, anti-angiogenesis immunotherapy, endocrine therapy. Accordingly, themselves downstream effectors and/or signaling pathways targets for optimizing sensitivity anti-cancer therapies. This review aims provide a detailed landscape role that play in conferring different cancers underlying mechanisms. The translational perspectives individualized treatment malignant tumors also discussed.

Language: Английский

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Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 22, 2023

Abstract The desmoplastic stroma in solid tumors presents a formidable challenge to immunotherapies that rely on endogenous or adoptively transferred T cells, however, the mechanisms are poorly understood. To define involved, here we treat established pancreatic with CAR cells directed fibroblast activation protein (FAP), an enzyme highly overexpressed subset of cancer-associated fibroblasts (CAFs). Depletion FAP + CAFs results loss structural integrity matrix. This renders these treatment-resistant cancers susceptible subsequent treatment tumor antigen (mesothelin)-targeted and anti-PD-1 antibody therapy. Mechanisms include overcoming stroma-dependent restriction cell extravasation and/or perivascular invasion, reversing immune exclusion, relieving suppression, altering landscape by reducing myeloid accumulation increasing CD8 NK infiltration. These data provide strong rationale for combining stroma- malignant cell-targeted therapies be tested clinical trials.

Language: Английский

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The advent of immune stimulating CAFs in cancer

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(4), P. 258 - 269

Published: Feb. 17, 2023

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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Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 7, 2024

Abstract Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer more challenging and may be unresponsive to conventional therapy. Immunotherapy crucial for treating but its resistance a major limitation. tumor microenvironment (TME) vital in modulating immunotherapy response. Various microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), are involved TME modulation cause resistance. This review highlights role stromal microenvironment, including involvement CAF-TAM interaction, alteration metabolism leading failure, other latest strategies, high throughput genomic screening, single-cell spatial omics techniques identifying immune genes regulating emphasizes therapeutic approach overcome through CAF reprogramming, TAM polarization, metabolism, alterations.

Language: Английский

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Cold and hot tumors: from molecular mechanisms to targeted therapy

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

Published: Oct. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Language: Английский

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