scholarly journals Identifying cancer-associated fibroblasts as emerging targets for hepatocellular carcinoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jie Zhang ◽  
Chaoyu Gu ◽  
Qianqian Song ◽  
Mengqi Zhu ◽  
Yuqing Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Vasculogenic Mimicry ◽  
Cancer Associated Fibroblasts ◽  
Biological Functions ◽  
Ecm Remodeling ◽  
Downstream Signaling ◽  
Cellular Origin ◽  
Suppressive Phenotype

Abstract The tumor microenvironment (TME) is a complex multicellular functional compartment that includes fibroblasts, myofibroblasts, endothelial cells, immune cells, and extracellular matrix (ECM) elements. The microenvironment provides an optimum condition for the initiation, growth, and dissemination of hepatocellular carcinoma (HCC). As one of the critical and abundant components in tumor microenvironment, cancer-associated fibroblasts (CAFs) have been implicated in the progression of HCC. Through secreting various growth factors and cytokines, CAFs contribute to the ECM remodeling, stem features, angiogenesis, immunosuppression, and vasculogenic mimicry (VM), which reinforce the initiation and development of HCC. In order to restrain the CAFs-initiated HCC progression, current strategies include targeting specific markers, engineering CAFs with tumor-suppressive phenotype, depleting CAFs’ precursors, and repressing the secretions or downstream signaling. In this review, we update the emerging understanding of CAFs in HCC, with particular emphasis on cellular origin, phenotypes, biological functions and targeted strategies. It provides insights into the targeting CAFs for HCC treatment.

scholarly journals Heterogeneity of cancer-associated fibroblasts and roles in the progression, prognosis, and therapy of hepatocellular carcinoma

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Zeli Yin ◽  
Chengyong Dong ◽  
Keqiu Jiang ◽  
Zhe Xu ◽  
Rui Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stromal Cell ◽  
Causes Of Death ◽  
Therapeutic Strategies ◽  
Research Topic ◽  
Cancer Associated Fibroblasts ◽  
Biological Functions ◽  
Cell Type ◽  
Cellular Origin ◽  
Heterogeneous Tissue

Abstract Hepatocellular carcinoma (HCC) is a lethal disease, and recurrence and metastasis are the major causes of death in HCC patients. Cancer-associated fibroblasts (CAFs), a major stromal cell type in the HCC microenvironment, promote HCC progression, and have gradually become a hot research topic in HCC-targeted therapy. This review comprehensively describes and discusses the heterogeneous tissue distribution, cellular origin, phenotype, and biological functions of HCC-associated fibroblasts. Furthermore, the possible use of CAFs for predicting HCC prognosis and in targeted therapeutic strategies is discussed, highlighting the critical roles of CAFs in HCC progression, diagnosis, and therapy.

scholarly journals Mining TCGA Database for Tumor Microenvironment-Related Genes of Prognostic Value in Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Zhenfeng Deng ◽  
Jilong Wang ◽  
Banghao Xu ◽  
Zongrui Jin ◽  
Guolin Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Malignant Tumors ◽  
Public Access ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Protein Protein Interaction ◽  
Potential Association ◽  
Poor Outcomes

Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies. Recent studies reveal that tumor microenvironment (TME) components significantly affect HCC growth and progression, particularly the infiltrating stromal and immune cells. Thus, mining of TME-related biomarkers is crucial to improve the survival of patients with HCC. Public access of The Cancer Genome Atlas (TCGA) database allows convenient performance of gene expression-based analysis of big data, which contributes to the exploration of potential association between genes and prognosis of a variety of malignancies, including HCC. The “Estimation of STromal and Immune cells in MAlignant Tumors using Expression data” algorithm renders the quantification of the stromal and immune components in TME possible by calculating the stromal and immune scores. Differentially expressed genes (DEGs) were screened by dividing the HCC cohort of TCGA database into high- and low-score groups according to stromal and immune scores. Further analyses of functional enrichment and protein-protein interaction networks show that the DEGs are mainly involved in immune response, cell adhesion, and extracellular matrix. Finally, seven DEGs have significant association with HCC poor outcomes. These genes contain FABP3, GALNT5, GPR84, ITGB6, MYEOV, PLEKHS1, and STRA6 and may be candidate biomarkers for HCC prognosis.

scholarly journals Nanoparticle-based delivery systems modulate the tumor microenvironment in pancreatic cancer for enhanced therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ming Jia ◽  
Dan Zhang ◽  
Chunxiang Zhang ◽  
Chunhong Li
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Malignant Tumors ◽  
Treatment Strategies ◽  
Delivery Systems ◽  
Cancer Microenvironment ◽  
Cancer Associated Fibroblasts ◽  
Hypoxic Environment ◽  
Promising Therapeutic Approach

AbstractPancreatic cancer is one of the most lethal malignant tumors with a low survival rate, partly because the tumor microenvironment (TME), which consists of extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), immune cells, and vascular systems, prevents effective drug delivery and chemoradiotherapy. Thus, modulating the microenvironment of pancreatic cancer is considered a promising therapeutic approach. Since nanoparticles are one of the most effective cancer treatment strategies, several nano-delivery platforms have been developed to regulate the TME and enhance treatment. Here, we summarize the latest advances in nano-delivery systems that alter the TME in pancreatic cancer by depleting ECM, inhibiting CAFs, reversing immunosuppression, promoting angiogenesis, or improving the hypoxic environment. We also discuss promising new targets for such systems. This review is expected to improve our understanding of how to modulate the pancreatic cancer microenvironment and guide the development of new therapies. Graphical Abstract

scholarly journals Cancer-Associated Fibroblast Heterogeneity: A Factor That Cannot Be Ignored in Immune Microenvironment Remodeling

2021 ◽  
Vol 12 ◽  
Author(s):  
Pei-Yu Chen ◽  
Wen-Fei Wei ◽  
Hong-Zhen Wu ◽  
Liang-Sheng Fan ◽  
Wei Wang
Keyword(s):  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Immune Regulation ◽  
Stromal Cells ◽  
Cancer Associated Fibroblasts ◽  
Immune Microenvironment ◽  
Cancer Associated Fibroblast ◽  
Different Origins ◽  
Fibroblast Heterogeneity

Cancer-associated fibroblasts (CAFs) are important, highly heterogeneous components of the tumor extracellular matrix that have different origins and express a diverse set of biomarkers. Different subtypes of CAFs participate in the immune regulation of the tumor microenvironment (TME). In addition to their role in supporting stromal cells, CAFs have multiple immunosuppressive functions, via membrane and secretory patterns, against anti-tumor immunity. The inhibition of CAFs function and anti-TME therapy targeting CAFs provides new adjuvant means for immunotherapy. In this review, we outline the emerging understanding of CAFs with a particular emphasis on their origin and heterogeneity, different mechanisms of their regulation, as well as their direct or indirect effect on immune cells that leads to immunosuppression.

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

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaoqi Mao ◽  
Jin Xu ◽  
Wei Wang ◽  
Chen Liang ◽  
Jie Hua ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Immune Cell ◽  
Critical Role ◽  
Cancer Associated Fibroblasts ◽  
Cell Of Origin ◽  
Future Perspectives ◽  
Immune Microenvironment ◽  
New Findings ◽  
Essential Components

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

scholarly journals Interaction between Fibroblasts and Immune Cells Following DNA Damage Induced by Ionizing Radiation

2020 ◽  
Author(s):  
Kalaiyarasi Ragunathan ◽  
Nikki Lyn Esnardo Upfold ◽  
Valentyn Oksenych
Keyword(s):  
Dna Damage ◽  
Tumor Microenvironment ◽  
Ionizing Radiation ◽  
Immune Cells ◽  
Mammalian Cells ◽  
Cancer Associated Fibroblasts ◽  
Cell Type ◽  
Dna Damages ◽  
Damage Response ◽  
High Doses

Cancer-associated fibroblasts (CAF) form the basis of tumor microenvironment and possess immunomodulatory functions by interacting with other cells surrounding tumor, including T lymphocytes, macrophages, dendritic cells and natural killer cells. Ionizing radiation is a broadly-used method in radiotherapy to target tumors. In mammalian cells, ionizing radiation induces various types of DNA damages and DNA damage response. Being unspecific, radiotherapy affects all the cells in tumor microenvironment, including the tumor itself, CAFs and immune cells. CAFs are extremely radio-resistant and do not initiate apoptosis even at high doses of radiation. However, following radiation, CAFs become senescent and produce a distinct combination of immunoregulatory molecules. Radiosensitivity of immune cells varies depending on the cell type due to inefficient DNA repair in, for example, monocytes and granulocytes. In this minireview, we are summarizing recent findings on the interaction between CAF, ionizing radiation and immune cells in the tumor microenvironment.

scholarly journals Identification of Novel Tumor Microenvironment-Related Long Noncoding RNAs to Determine the Prognosis and Response to Immunotherapy of Hepatocellular Carcinoma Patients

2021 ◽  
Vol 8 ◽  
Author(s):  
Shenglan Huang ◽  
Jian Zhang ◽  
Xiaolan Lai ◽  
Lingling Zhuang ◽  
Jianbing Wu
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Risk Model ◽  
Cox Regression ◽  
Risk Group ◽  
Low Risk ◽  
Kaplan Meier ◽  
Treatment Responses

Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with poor prognosis. The tumor microenvironment (TME) plays a vital role in HCC progression. Thus, this research was designed to analyze the correlation between the TME and the prognosis of HCC patients and to construct a TME-related long noncoding RNA (lncRNA) signature to determine HCC patients’ prognosis and response to immunotherapy.Methods: We assessed the stromal–immune–estimate scores within the HCC microenvironment using the ESTIMATE (Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data) algorithm based on The Cancer Genome Atlas database, and their associations with survival and clinicopathological parameters were also analyzed. Thereafter, differentially expressed lncRNAs were filtered out according to the immune and stromal scores. Cox regression analysis was performed to build a TME-related lncRNA risk signature. Kaplan–Meier analysis was used to explore the prognostic value of the risk signature. Furthermore, we explored the biological functions and immune microenvironment features in the high- and low-risk groups. Lastly, we probed the association of the risk model with treatment responses to immune checkpoint inhibitors (ICIs) in HCC.Results: The stromal, immune, and estimate scores were obtained utilizing the ESTIMATE algorithm for patients with HCC. Kaplan–Meier analysis showed that high scores were significantly correlated with better prognosis in HCC patients. Six TME-related lncRNAs were screened to construct the prognostic model. The Kaplan–Meier curves suggested that HCC patients with low risk had better prognosis than those with high risk. Receiver operating characteristic (ROC) curve and Cox regression analyses indicated that the risk model could predict HCC survival exactly and independently. Functional enrichment analysis revealed that some tumor- and immune-related pathways were activated in the high-risk group. We also revealed that some immune cells, which were important in enhancing immune responses toward cancer, were significantly increased in the low-risk group. In addition, there was a close correlation between ICIs and the risk signature, which can be used to predict the treatment responses of HCC patients.Conclusion: We analyzed the influence of the stromal, immune, and estimate scores on the prognosis of HCC patients. A novel TME-related lncRNA risk model was established, which could be effectively applied as an independent prognostic biomarker and predictor of ICIs for HCC patients.

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