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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Clinical and therapeutic relevance of cancer-associated fibroblasts

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 18(12), P. 792 - 804

Published: Sept. 6, 2021

Language: Английский

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Applications of single-cell sequencing in cancer research: progress and perspectives

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: June 9, 2021

Single-cell sequencing, including genomics, transcriptomics, epigenomics, proteomics and metabolomics is a powerful tool to decipher the cellular molecular landscape at single-cell resolution, unlike bulk which provides averaged data. The use of sequencing in cancer research has revolutionized our understanding biological characteristics dynamics within lesions. In this review, we summarize emerging technologies recent progress obtained by information related landscapes malignant cells immune cells, tumor heterogeneity, circulating underlying mechanisms behaviors. Overall, prospects facilitating diagnosis, targeted therapy prognostic prediction among spectrum tumors are bright. near future, advances will undoubtedly improve highlight potential precise therapeutic targets for patients.

Language: Английский

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Cancer-associated fibroblasts in the single-cell era

Nature Cancer, Journal Year: 2022, Volume and Issue: 3(7), P. 793 - 807

Published: July 26, 2022

Language: Английский

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Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment

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

Published: Nov. 4, 2022

Abstract Cancer-associated fibroblasts (CAFs) are the predominant components of tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different types. Here, we perform pan-cancer analysis 226 samples 10 solid types to profile TME at single-cell resolution, illustrating commonalities/plasticity heterogenous CAFs. Activation trajectory major CAF is divided into three states, exhibiting distinct interactions with other cell components, relating prognosis immunotherapy. Moreover, minor represent alternative origin from (e.g., endothelia macrophages). Particularly, presentation endothelial-to-mesenchymal transition CAF, which may interact proximal SPP 1 + tumor-associated macrophages, implicated in survival stratifications. Our study comprehensively profiles shared dynamics CAFs, highlight heterogeneity plasticity Browser integrated information available https://gist-fgl.github.io/sc-caf-atlas/ .

Language: Английский

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Biomarkers for cancer-associated fibroblasts

Biomarker Research, Journal Year: 2020, Volume and Issue: 8(1)

Published: Nov. 11, 2020

Cancer-associated fibroblasts (CAFs) are the key component of tumor stromal. High heterogeneity CAFs reflects in their origin, phenotype and function. Biological function which can be suggested by biomarkers distinct CAF subgroups may different, even opposite, just like water fire. Identifying subpopulations expressing different reconciling relationship "water fire" among subsets a breakthrough therapy. Herein, we briefly summarize commonly used or newly identified for terms features potential clinical benefits.

Language: Английский

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Inflammation-Induced Tumorigenesis and Metastasis

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(11), P. 5421 - 5421

Published: May 21, 2021

Inflammation, especially chronic inflammation, plays a pivotal role in tumorigenesis and metastasis through various mechanisms is now recognized as hallmark of cancer an attractive therapeutic target cancer. In this review, we discuss recent advances molecular how inflammation promotes suppresses anti-tumor immunity types solid tumors, including esophageal, gastric, colorectal, liver, pancreatic well hematopoietic malignancies.

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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Tumor heterogeneity reshapes the tumor microenvironment to influence drug resistance

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(7), P. 3019 - 3033

Published: Jan. 1, 2022

Tumor heterogeneity is one of the hallmarks cancer and a challenge in field oncology.Tumor main cause drug resistance, leading to therapeutic failure.Mechanically, tumor either directly affects targets or shapes microenvironment (TME) by defining transcriptomic phenotypic profiles influence resistance.Tumor evolves spatially temporally during development, constant reprogramming TME.Advances molecular profiling technologies precision oncology platforms have allowed us uncover impact on resistance context TME.In this review, we focus processes which genomic mutations drive mechanisms through reprograms TME affect patient prognosis.

Language: Английский

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Revealing the transcriptional heterogeneity of organ‐specific metastasis in human gastric cancer using single‐cell RNA Sequencing

Clinical and Translational Medicine, Journal Year: 2022, Volume and Issue: 12(2)

Published: Feb. 1, 2022

Abstract Background Deciphering intra‐ and inter‐tumoural heterogeneity is essential for understanding the biology of gastric cancer (GC) its metastasis identifying effective therapeutic targets. However, characteristics different organ‐tropism metastases GC are largely unknown. Methods Ten fresh human tissue samples from six patients, including primary tumour adjacent non‐tumoural organs or tissues (liver, peritoneum, ovary, lymph node) were evaluated using single‐cell RNA sequencing. Validation experiments performed histological assays bulk transcriptomic datasets. Results Malignant epithelial subclusters associated with invasion features, intraperitoneal propensity, epithelial–mesenchymal transition‐induced stem cell phenotypes, dormancy‐like discovered. High expression first three subcluster‐associated genes displayed worse overall survival than those low in a cohort containing 407 samples. Immune stromal cells exhibited cellular created pro‐tumoural immunosuppressive microenvironment. Furthermore, 20‐gene signature node‐derived exhausted CD8 + T was acquired to forecast node validated cohorts. Additionally, although anti‐NKG2A (KLRC1) antibody have not been used treat patients even clinical trials, we uncovered only malignant but one endothelial subcluster, mucosal‐associated invariant cells, cell‐like B plasmacytoid dendritic macrophages, monocytes, neutrophils may contribute HLA‐E‐KLRC1/KLRC2 interaction cytotoxic/exhausted and/or natural killer (NK) suggesting novel opportunities GC. our findings suggested that PD‐1 might predict responses blockade therapy Conclusions This study provided insights into heterogeneous microenvironment tumours organ‐specific provide support precise diagnosis treatment.

Language: Английский

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