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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Tumor microenvironment complexity and therapeutic implications at a glance

Cell Communication and Signaling, Journal Year: 2020, Volume and Issue: 18(1)

Published: April 7, 2020

Abstract The dynamic interactions of cancer cells with their microenvironment consisting stromal (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity cell, clonal evolution increase multidrug resistance ending in cell progression metastasis. reciprocal cell-cell/ECM interaction tumor hijacking non-malignant force lose function acquire new phenotypes that promote development invasion cells. Understanding underlying cellular molecular mechanisms governing these can be used as a novel strategy indirectly disrupt interplay contribute efficient safe therapeutic strategies fight cancer. Furthermore, tumor-derived circulating materials also diagnostic tools precisely predict monitor outcome therapy. This review evaluates such potentials various advanced models, focus on 3D systems well lab-on-chip devices.

Language: Английский

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Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer

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

Published: April 1, 2022

Abstract Colorectal cancer (CRC) is among the most common malignancies with limited treatments other than surgery. The tumor microenvironment (TME) profiling enables discovery of potential therapeutic targets. Here, we profile 54,103 cells from and adjacent tissues to characterize cellular composition elucidate origin regulation tumor-enriched cell types in CRC. We demonstrate that tumor-specific FAP + fibroblasts SPP1 macrophages were positively correlated 14 independent CRC cohorts containing 2550 samples validate their close localization by immuno-fluorescent staining spatial transcriptomics. This interaction might be regulated chemerin, TGF-β, interleukin-1, which would stimulate formation immune-excluded desmoplasic structure limit T infiltration. Furthermore, find patients high or expression achieved less benefit an anti-PD-L1 therapy cohort. Our results provide a strategy disrupting improve immunotherapy.

Language: Английский

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Cancer-associated fibroblasts and their influence on tumor immunity and immunotherapy

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Dec. 28, 2020

Fibroblasts play an essential role in organogenesis and the integrity of tissue architecture function. Growth most solid tumors is dependent upon remodeling ‘stroma’, composed cancer-associated fibroblasts (CAFs) extracellular matrix (ECM), which plays a critical tumor initiation, progression, metastasis, therapeutic resistance. Recent studies have clearly established that potent immunosuppressive activity stroma major mechanism by can promote progression confer resistance to immune-based therapies. Herein, we review recent advances identifying stroma-dependent mechanisms regulate inflammation antitumor immunity, particular, interactions between immune cells. We also potential therapies for current advancements stroma-targeted

Language: Английский

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Cancer-associated fibroblasts in desmoplastic tumors: emerging role of integrins

Seminars in Cancer Biology, Journal Year: 2019, Volume and Issue: 62, P. 166 - 181

Published: Aug. 12, 2019

The tumor microenvironment (TME) is a complex meshwork of extracellular matrix (ECM) macromolecules filled with collection cells including cancer-associated fibroblasts (CAFs), blood vessel associated smooth muscle cells, pericytes, endothelial mesenchymal stem and variety immune cells. In tumors the homeostasis governing ECM synthesis turnover disturbed resulting in abnormal formation excessive fibrillar collagen accumulations varying stiffness organization. opens up for new types paracrine, cell-cell cell-ECM interactions large consequences growth, angiogenesis, metastasis, suppression resistance to treatments. As main producer paracrine signals CAF central cell type these events. Whereas signaling has been extensively studied context tumor-stroma interactions, nature numerous integrin-mediated occurring TME remains understudied. this review we will discuss dissect role known potential TME, during both tumorigenesis chemoresistance-induced events, special focus on "interaction landscape" desmoplastic breast, lung pancreatic cancers. an example multifaceted mode action stromal receptor integrin α11β1, summarize our current understanding CAF-expressed three types.

Language: Английский

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Cancer-associated fibroblasts: overview, progress, challenges, and directions

Cancer Gene Therapy, Journal Year: 2021, Volume and Issue: 28(9), P. 984 - 999

Published: March 12, 2021

Language: Английский

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Cancer associated-fibroblast-derived exosomes in cancer progression

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

Published: Dec. 1, 2021

To identify novel cancer therapies, the tumor microenvironment (TME) has received a lot of attention in recent years particular with advent clinical successes achieved by targeting immune checkpoint inhibitors (ICIs). The TME consists multiple cell types that are embedded extracellular matrix (ECM), including cells, endothelial cells and associated fibroblasts (CAFs), which communicate each other during progression. CAFs dominant heterogeneous type within pivotal role controlling invasion metastasis, evasion, angiogenesis chemotherapy resistance. mediate their effects part remodeling ECM secreting soluble factors vesicles. Exosomes subtype vesicles (EVs), contain various biomolecules such as nucleic acids, lipids, proteins. exosomes can be transmitted from one to another cell, thereby affect behavior receiving cell. As also present circulation, contents explored biomarkers for diagnosis prognosis patients. In this review, we concentrate on CAFs-derived communication between TME. First, introduce roles tumorigenesis. Thereafter, discuss ways interplay TME, focus exosomes. Then, elaborate mechanisms contribute progression, well impact We conclude discussing aspects deserve further investigation, emerging insights into making treatment inhibitor blockade more efficient.

Language: Английский

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Prognostic and Predictive Molecular Biomarkers for Colorectal Cancer: Updates and Challenges

Cancers, Journal Year: 2020, Volume and Issue: 12(2), P. 319 - 319

Published: Jan. 30, 2020

Colorectal cancer (CRC) is a leading cause of death among patients. This heterogeneous disease characterized by alterations in multiple molecular pathways throughout its development. Mutations RAS, along with the mismatch repair gene deficiency, are currently routinely tested clinics. Such biomarkers provide information for patient risk stratification and choice best treatment options. Nevertheless, reliable powerful prognostic markers that can identify "high-risk" CRC patients, who might benefit from adjuvant chemotherapy, early stages, missing. To bridge this gap, genomic has increasingly gained interest as potential method determining recurrence. However, due to several limitations gene-based signatures, these have not yet been clinically implemented. In review, we describe different clinical use CRC, highlight new become indispensable over next years, discuss recently developed expression-based tests challenges biomarker research.

Language: Английский

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The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

Cancers, Journal Year: 2021, Volume and Issue: 13(18), P. 4720 - 4720

Published: Sept. 21, 2021

Cancer-associated fibroblasts (CAFs) play a key role in cancer progression by contributing to extracellular matrix (ECM) deposition and remodeling, extensive crosstalk with cells, epithelial-to-mesenchymal transition (EMT), invasion, metastasis, therapy resistance. As metastasis is main reason for cancer-related deaths, it crucial understand the of CAFs this process. Colorectal (CRC) heterogeneous disease lethality especially common subtype CRC high stromal infiltration. A component stroma cancer-associated (CAFs). To provide new perspectives research on CAF-targeted therapeutics, CRC, we discuss mechanisms, crosstalk, functions involved CAF-mediated protection. This summary can serve as framework future studies elucidating these roles CAFs.

Language: Английский

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Spatial Positioning and Matrix Programs of Cancer-Associated Fibroblasts Promote T-cell Exclusion in Human Lung Tumors

Cancer Discovery, Journal Year: 2022, Volume and Issue: 12(11), P. 2606 - 2625

Published: Aug. 26, 2022

Abstract It is currently accepted that cancer-associated fibroblasts (CAF) participate in T-cell exclusion from tumor nests. To unbiasedly test this, we used single-cell RNA sequencing coupled with multiplex imaging on a large cohort of lung tumors. We identified four main CAF populations, two which are associated exclusion: (i) MYH11+αSMA+ CAF, present early-stage tumors and form single cell layer lining cancer aggregates, (ii) FAP+αSMA+ appear more advanced organize patches within the stroma or multiple layers around Both populations orchestrate particular structural tissue organization through dense aligned fiber deposition compared T cell–permissive CAF. Yet they produce distinct matrix molecules, including collagen IV (MYH11+αSMA+ CAF) XI/XII (FAP+αSMA+ CAF). Hereby, uncovered unique molecular programs driving marginalization, whose targeting should increase immunotherapy efficacy patients bearing cell–excluded Significance: The cellular marginalization solid remain unclear. Here, describe human demonstrate importance pairing spatial analysis microenvironment, prerequisite to developing new strategies cell–excluding See related commentary by Sherman, p. 2501. This article highlighted In Issue feature, 2483

Language: Английский

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