scholarly journals Acidic and Hypoxic Microenvironment in Melanoma: Impact of Tumour Exosomes on Disease Progression

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3311
Author(s):  
Zaira Boussadia ◽  
Adriana Rosa Gambardella ◽  
Fabrizio Mattei ◽  
Isabella Parolini
Keyword(s):  
Malignant Melanoma ◽  
Immune Cells ◽  
Stromal Cells ◽  
Immune Surveillance ◽  
Tumour Microenvironment ◽  
Response To Treatment ◽  
Malignant Phenotype ◽  
Hypoxic Conditions ◽  
Melanoma Diagnosis

The mechanisms of melanoma progression have been extensively studied in the last decade, and despite the diagnostic and therapeutic advancements pursued, malignant melanoma still accounts for 60% of skin cancer deaths. Therefore, research efforts are required to better define the intercellular molecular steps underlying the melanoma development. In an attempt to represent the complexity of the tumour microenvironment (TME), here we analysed the studies on melanoma in acidic and hypoxic microenvironments and the interactions with stromal and immune cells. Within TME, acidity and hypoxia force melanoma cells to adapt and to evolve into a malignant phenotype, through the cooperation of the tumour-surrounding stromal cells and the escape from the immune surveillance. The role of tumour exosomes in the intercellular crosstalk has been generally addressed, but less studied in acidic and hypoxic conditions. Thus, this review aims to summarize the role of acidic and hypoxic microenvironment in melanoma biology, as well as the role played by melanoma-derived exosomes (Mexo) under these conditions. We also present a perspective on the characteristics of acidic and hypoxic exosomes to disclose molecules, to be further considered as promising biomarkers for an early detection of the disease. An update on the use of exosomes in melanoma diagnosis, prognosis and response to treatment will be also provided and discussed.

scholarly journals The dynamic behavior of lipid droplets in the pre-metastatic niche

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chunliang Shang ◽  
Jie Qiao ◽  
Hongyan Guo
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Lipid Droplets ◽  
Metastatic Tumor ◽  
Current Evidence ◽  
Biological Functions ◽  
Metastatic Niche ◽  
Niche Formation

AbstractThe pre-metastatic niche is a favorable microenvironment for the colonization of metastatic tumor cells in specific distant organs. Lipid droplets (LDs, also known as lipid bodies or adiposomes) have increasingly been recognized as lipid-rich, functionally dynamic organelles within tumor cells, immune cells, and other stromal cells that are linked to diverse biological functions and human diseases. Moreover, in recent years, several studies have described the indispensable role of LDs in the development of pre-metastatic niches. This review discusses current evidence related to the biogenesis, composition, and functions of LDs related to the following characteristics of the pre-metastatic niche: immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, reprogramming. We also address the function of LDs in mediating pre-metastatic niche formation. The potential of LDs as markers and targets for novel antimetastatic therapies will be discussed.

scholarly journals Correlation Between Immune Lymphoid Cells and Plasmacytoid Dendritic Cells in Human Colon Cancer

2020 ◽  
Author(s):  
Jing Wu ◽  
Hang Cheng ◽  
Tete Li ◽  
Helei Wang ◽  
Guoxia Zang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Dendritic Cells ◽  
Rna Sequencing ◽  
Immune Cells ◽  
Human Colon ◽  
Tumour Microenvironment ◽  
Plasmacytoid Dendritic Cells ◽  
Lymphoid Cells ◽  
Human Colon Cancer

Abstract Background: Innate lymphoid cells (ILCs), so far studied mostly in mouse models, are important tissue-resident innate immune cells that play important roles in the colorectal cancer microenvironment and maintain the mucosal tissue homeostasis. Plasmacytoid dendritic cells (pDCs) present complexity in various tumour types and are correlated with poor prognosis. pDCs can promote HIV-1–induced group 3 ILC (ILC3) depletion through the CD95 pathway. However, the role of ILC3s in human colon cancer and their correlation with other immune cells, especially pDCs, remain unclear. Methods: We characterised ILCs and pDCs in the tumour microenvironment of 58 colon cancer patients by flow cytometry and selected three patients for RNA sequencing. Results: ILC3s were negatively correlated, and pDCs were positively correlated, with cancer pathological grade. There was a negative correlation between the numbers of ILC3s and pDCs in tumour tissues. RNA sequencing confirmed the correlations between ILC3s and pDCs and highlighted the potential function of many ILC- and pDC-associated differentially expressed genes in the regulation of tumour immunity. pDCs can induce apoptosis of ILC3s through the CD95 pathway in the tumour microenvironment. Conclusions: One of the interactions between ILC3s and pDCs is via the CD95 pathway, which may help explain the role of ILC3s in colon cancer.

scholarly journals The role of the tumour microenvironment in the angiogenesis of pituitary tumours

Endocrine ◽  
2020 ◽  
Vol 70 (3) ◽  
pp. 593-606
Author(s):  
Pedro Marques ◽  
Sayka Barry ◽  
Eivind Carlsen ◽  
David Collier ◽  
Amy Ronaldson ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Immune Cells ◽  
Microvessel Density ◽  
Tumour Microenvironment ◽  
Vascular Morphology ◽  
Hla Dr ◽  
M1 Macrophage ◽  
Culture Supernatants

Abstract Purpose Angiogenesis has been studied in pituitary neuroendocrine tumours (PitNETs), but the role of the tumour microenvironment (TME) in regulating PitNET angiogenesis remains unknown. We aimed to characterise the role of TME components in determining the angiogenetic PitNET profile, focusing on immune cells and tumour-derived cytokines. Methods Immune cells were studied by immunohistochemistry in 24 human PitNETs (16 non-functioning-PitNETs (NF-PitNETs) and 8 somatotrophinomas): macrophages (CD68, CD163, HLA-DR), cytotoxic (CD8) and T helper (CD4) lymphocytes, regulatory T cells (FOXP3), B cells (CD20) and neutrophils (neutrophil elastase); endothelial cells were assessed with CD31. Five normal pituitaries (NP) were included for comparison. Microvessel density and vascular morphology were estimated with ImageJ. The cytokine secretome from these PitNETs were assessed on culture supernatants using a multiplex immunoassay panel. Results Microvessel density/area was higher in NP than PitNETs, which also had rounder and more regular vessels. NF-PitNETs had vessels of increased calibre compared to somatotrophinomas. The M2:M1 macrophage ratio correlated with microvessel area. PitNETs with more CD4+ T cells had higher microvessel area, while tumours with more FOXP3+ cells were associated with lower microvessel density. PitNETs with more B cells had rounder vessels. Of the 42 PitNET-derived cytokines studied, CCL2, CXCL10 and CX3CL1 correlated with microvessel density and vessel architecture parameters. Conclusions M2 macrophages appear to play a role in PitNET neovascularisation, while B, CD4+ and FOXP3+ lymphocytes, as well as non-cellular TME elements such as CCL2, CXCL10 and CX3CL1, may also modulate the angiogenesis of PitNETs.

scholarly journals Energy metabolism manipulates the fate and function of tumour myeloid-derived suppressor cells

2019 ◽  
Vol 122 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Cong Hu ◽  
Bo Pang ◽  
Guangzhu Lin ◽  
Yu Zhen ◽  
Huanfa Yi
Keyword(s):  
Metabolic Pathways ◽  
Immune Surveillance ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Metabolic Energy ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Responses ◽  
And Function ◽  
Promote Tumour Development

AbstractIn recent years, a large number of studies have been carried out in the field of immune metabolism, highlighting the role of metabolic energy reprogramming in altering the function of immune cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells generated during a large array of pathological conditions, such as cancer, inflammation, and infection, and show remarkable ability to suppress T-cell responses. These cells can also change their metabolic pathways in response to various pathogen-derived or inflammatory signals. In this review, we focus on the roles of glucose, fatty acid (FA), and amino acid (AA) metabolism in the differentiation and function of MDSCs in the tumour microenvironment, highlighting their potential as targets to inhibit tumour growth and enhance tumour immune surveillance by the host. We further highlight the remaining gaps in knowledge concerning the mechanisms determining the plasticity of MDSCs in different environments and their specific responses in the tumour environment. Therefore, this review should motivate further research in the field of metabolomics to identify the metabolic pathways driving the enhancement of MDSCs in order to effectively target their ability to promote tumour development and progression.

scholarly journals Exploring the key communicator role of exosomes in cancer microenvironment through proteomics

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
HuiSu Kim ◽  
Dong Wook Kim ◽  
Je-Yoel Cho
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Diagnosis ◽  
Stromal Cells ◽  
Cancer Biology ◽  
Immune Surveillance ◽  
Cancer Microenvironment ◽  
Promote Tumor Growth ◽  
Therapeutic Tools ◽  
Intercellular Communications

ABSTRACT There have been many attempts to fully understand the mechanism of cancer behavior. Yet, how cancers develop and metastasize still remain elusive. Emerging concepts of cancer biology in recent years have focused on the communication of cancer with its microenvironment, since cancer cannot grow and live alone. Cancer needs to communicate with other cells for survival, and thus they secrete various messengers, including exosomes that contain many proteins, miRNAs, mRNAs, etc., for construction of the tumor microenvironment. Moreover, these intercellular communications between cancer and its microenvironment, including stromal cells or distant cells, can promote tumor growth, metastasis, and escape from immune surveillance. In this review, we summarized the role of proteins in the exosome as communicators between cancer and its microenvironment. Consequently, we present cancer specific exosome proteins and their unique roles in the interaction between cancer and its microenvironment. Clinically, these exosomes might provide useful biomarkers for cancer diagnosis and therapeutic tools for cancer treatment.

scholarly journals Cancer Stem Cells: Emerging Key Players in Immune Evasion of Cancers

2021 ◽  
Vol 9 ◽  
Author(s):  
Martina Mang Leng Lei ◽  
Terence Kin Wah Lee
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Immune Cells ◽  
Immune Surveillance ◽  
Suppressor Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Treg Cells ◽  
Undifferentiated Cancer

Cancer stem cells (CSCs) are subpopulations of undifferentiated cancer cells within the tumor bulk that are responsible for tumor initiation, recurrence and therapeutic resistance. The enhanced ability of CSCs to give rise to new tumors suggests potential roles of these cells in the evasion of immune surveillance. A growing body of evidence has described the interplay between CSCs and immune cells within the tumor microenvironment (TME). Recent data have shown the pivotal role of some major immune cells in driving the expansion of CSCs, which concurrently elicit evasion of the detection and destruction of various immune cells through a number of distinct mechanisms. Here, we will discuss the role of immune cells in driving the stemness of cancer cells and provide evidence of how CSCs evade immune surveillance by exerting their effects on tumor-associated macrophages (TAMs), dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), T-regulatory (Treg) cells, natural killer (NK) cells, and tumor-infiltrating lymphocytes (TILs). The knowledge gained from the interaction between CSCs and various immune cells will provide insight into the mechanisms by which tumors evade immune surveillance. In conclusion, CSC-targeted immunotherapy emerges as a novel immunotherapy strategy against cancer by disrupting the interaction between immune cells and CSCs in the TME.

scholarly journals Concise review: The role of cancer-derived exosomes in tumorigenesis and immune cell modulation

2020 ◽  
Vol 7 (12) ◽  
pp. 4158-4169
Author(s):  
Nhi Thao Huynh ◽  
Khuong Duy Pham ◽  
Nhat Chau Truong
Keyword(s):  
Cancer Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Vascular System ◽  
Immune Surveillance ◽  
Cell Communication ◽  
Tumor Formation ◽  
Concise Review ◽  
The Relationship

Exosomes are subcellular entities which were first discovered in the 1980s. Over the past decade, scientists have discovered that they carry components of genetic information that allow for cell-cell communication and cell targeting. Exosomes secreted by cancer cells are termed cancer-derived exosomes (CDEs), and play an important role in tumor formation and progression. Specifically, CDEs mediate the communication between cancer cells, as well as between cancer cells and other cells in the tumor microenvironment, including cancer-associated fibroblasts, endothelial cells, mesenchymal stem cells, and effector immune cells. Additionally, through the vascular system and body fluids, CDEs can modulate response to drugs, increase angiogenesis, stimulate proliferation, promote invasion and metastasis, and facilitate escape from immune surveillance. This review will discuss the relationship between cancer cells and other cells (particularly immune cells), as mediated through CDEs, as well as the subsequent impact on tumorigenesis and immunomodulation. Understanding the role of CDEs in tumorigenesis and immune cell modulation will help advance their utilization in the diagnosis, prognosis, and treatment of cancer.

scholarly journals Role of miRNAs in Melanoma Metastasis

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 326 ◽  
Author(s):  
Anna Gajos-Michniewicz ◽  
Malgorzata Czyz
Keyword(s):  
Target Genes ◽  
Selective Advantage ◽  
Tumour Microenvironment ◽  
Response To Treatment ◽  
Melanoma Metastasis ◽  
Liquid Biopsies ◽  
Tumour Metastasis ◽  
Multistep Process ◽  
Ecm Extracellular Matrix

Tumour metastasis is a multistep process. Melanoma is a highly aggressive cancer and metastasis accounts for the majority of patient deaths. microRNAs (miRNAs) are non-coding RNAs that affect the expression of their target genes. When aberrantly expressed they contribute to the development of melanoma. While miRNAs can act locally in the cell where they are synthesized, they can also influence the phenotype of neighboring melanoma cells or execute their function in the direct tumour microenvironment by modulating ECM (extracellular matrix) and the activity of fibroblasts, endothelial cells, and immune cells. miRNAs are involved in all stages of melanoma metastasis, including intravasation into the lumina of vessels, survival during circulation in cardiovascular or lymphatic systems, extravasation, and formation of the pre-metastatic niche in distant organs. miRNAs contribute to metabolic alterations that provide a selective advantage during melanoma progression. They play an important role in the development of drug resistance, including resistance to targeted therapies and immunotherapies. Distinct profiles of miRNA expression are detected at each step of melanoma development. Since miRNAs can be detected in liquid biopsies, they are considered biomarkers of early disease stages or response to treatment. This review summarizes recent findings regarding the role of miRNAs in melanoma metastasis.

Exosomes: Critical mediators of tumour microenvironment reprogramming

2020 ◽  
Vol 28 ◽  
Author(s):  
Rama Rao Malla ◽  
Gugalavath Shailender ◽  
Mohammad Amjad Kamal
Keyword(s):  
Cancer Progression ◽  
Stromal Cells ◽  
Vaccine Development ◽  
Cell Metabolism ◽  
Tumour Microenvironment ◽  
Cell Reprogramming ◽  
Chemotherapeutic Drugs ◽  
Metastatic Niche ◽  
Tumour Vasculature

: Tumour microenvironment (TME) is a resident of a variety of cells, which devoted to the heterogeneous population of the tumour. TME establishes a communication network for crosstalk and signalling between tumour cells, stroma, and other interstitial cells. The cross-communication drives the reprogramming of TME cells, which promote cancer progression and metastasis via diverse signalling pathways. Recently, TME-derived exosomes are recognized as critical communicators of TME cell reprogramming. This review addresses the role of TME-derived exosomes in the modulation of stroma, including reprogramming the stromal cells, ECM and tumour cell metabolism, as well as neoplastic transformation. Subsequently, we described the role of exosomes in pre-metastatic niche development, maintenance of stemness and tumour vasculature as well as development of drug resistance. We also explored tumour-derived exosomes in precision, including diagnosis, drug delivery, and vaccine development. We discussed the currently established bioengineered exosomes as carriers for chemotherapeutic drugs, RNAi molecules, and natural compounds. Finally, we presented tetraspanin and DNAbased precision methods for the quantification of tumour-derived exosomes. Overall, TME-derived exosome-mediated reprogramming of TME and precision strategies could illuminate the potential mechanisms for targeted therapeutic intervention.

CD247 Functions as a Prognostic Biomarker for Cutaneous Malignant Melanoma Based on the Analysis of Tumor-immune Microenvironment

2020 ◽  
Author(s):  
yi ma ◽  
Shu-Shu Chen ◽  
Yan-Yan Feng ◽  
Ru-Yi Ma ◽  
Huan-Liang Wang
Keyword(s):  
Survival Analysis ◽  
Malignant Melanoma ◽  
Immune Cells ◽  
Prognostic Biomarker ◽  
Tumour Microenvironment ◽  
Cutaneous Malignant Melanoma ◽  
Cox Proportional Hazards Model ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Hub Genes

Abstract Background: Cutaneous malignant melanoma (CMM) is among the most lethal cancers. The tumour microenvironment (TME) is closely linked with tumorigenesis, metastasis, and prognosis.Methods: We employed the ESTIMATE algorithm to calculate immune and stromal scores of malignant melanoma tissues from the Cancer Genome Atlas dataset, respectively, and determine core prognosis gene signature examined by COX proportional hazards model. Functional enrichment annotation, the Kyoto Encyclopedia of Genes and Genomes pathways, the Protein-Protein Interaction network, Weighted Gene Co-expression Network Analysis and overall survival analysis were used to formulate potential function of these genes that involved in immune-linked biological processes. CIBERSORT algorithm was used to estimate the abundances of immune cell types in CMM samples. Finally, the OncoLnc platform, the Gene Expression Profiling Interactive Analysis resources, and the Human Protein Atlas database were applied to validate our results. Results：908 differential expressed genes and ten hub genes were screened, and GO annotation indicated that immune response and inflammatory response were firmly involved in CMM tumorigenesis and progression. CD247, identified as the most significant prognostic biomarker, highly expressed in tumor samples and possessed a better prognosis than low expressed samples. The correlation analysis of immune cells infiltration unveiled that CD8+ T cell and Macrophages were intense significant to CMM patients' prognosis. Survival analysis suggested that ten hub genes and infiltrated immune cells are linked to the prognosis of CMM. ConnectiveMap analysis strongly indicated that L-securinine may be a promising candidate medicine for CMM patients.Conclusions: we deeply analyzed the immune-linked genes with the tumour microenvironment, and labeled CD247 as the most intriguing prognostic biomarker for CMM, which may bring better clinical outcomes for CMM patients.

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